Journal of Cosmology

Cosmology, 2009, Vol 1, 150-200
Peer Reviewed

Genetics and Evolution of
Life From Other Planets:
Viruses, Bacteria, Archae, Eukaryotes, Introns, Transposons, Exons, Conserved Genes, Silent Genes, Regulatory Genes, Whole Genome Duplication, Gene Expression, and Evolutionary Metamorphosis

Rhawn Joseph, Ph.D.
Cosmology.com

ABSTRACT

What has been described as "evolution" is under genetic regulatory control and is a form of metamorphosis (Evolutionary Metamorphosis), the replication of life forms which lived on other planets. The genetic endowment of all Earthly life can be traced to common ancestors, and these genes were obtained and inherited from creatures which lived on other worlds. This genetic inheritance included exons, introns, transposable elements, RNA, ribozomes, and the core genetic machinery for translating, expressing, and repeatedly duplicating genes and the entire genome. The first creatures to arrive on Earth acted as interplanetary genetic messengers, and were accompanied by viruses which served as intergalactic genetic libraries and depositories for genes which are held in storage. Once on Earth, prokaryotic and viral genes were initially combined to fashion the first eukaryotes and/or were donated and transferred to unicellular eukaryotes and subsequently expressed in response to biologically engineered environmental influences, often in busts of explosive evolutionary change. Viral genes interact with prokaryote genes which have been transferred to the eukaryote genome in a highly regulated, choreographed, coordinated manner, and which is often of direct benefit to the host. Viruses also insert RNA templates of DNA which are easily integrated with the genome of the host, selectively targeting specific hosts before or after they evolve. These templates match the host genome and existed prior to the evolution of the host, and this indicates the original source must have been an extraterrestrial host. Throughout the course of history these highly regulated interactions between viruses and prokaryote and eukaryote genes have guided the pace and trajectory of evolution, such as by turning genes on and off and releasing precoded genetic instructions. Human evolution has been shaped by repeated episodes of viral invasions and the injections of viral genes which interact with prokaryote genes in a purposeful manner. This inherited extraterrestrial genetic machinery has acted purposefully to coordinate gene duplication and expression, speciation, and evolutionary innovation, thereby giving rise to a genetically regulated progression leading from simple to complex creatures including woman and man.

1. THE EVOLUTION OF LIFE FROM OTHER PLANETS

There is only one logical, scientific explanation for the origin of Earthly life: Life on Earth came from life whose ancestry leads to other, more ancient worlds (Joseph 2000, 2009a,b,c, 2010; Joseph and Schild 2010a,b). As most scientists agree that modern day life can be traced to those who were the first to call Earth home, then our genetic heritage can also be traced to life which lived on other planets. Because all modern day life evolved from these genes, this also means that the evolution of life on Earth has also been impacted, guided, and even directed by these genes which were inherited from living creatures which long ago lived on other planets.

As detailed by Joseph and Schild (2010), life could not have begun on this planet for the following reasons: A) All the essential ingredients for creating life were missing on the new Earth, including, and especially oxygen, sugar, and phosphorus B) DNA and complex organic molecules would have been destroyed by the environment of the early Earth and even proto-organisms would not have been able to surive . C) Given the complexity of a single protein and a single macromolecule of DNA, statistically, there was not enough time to create a complex self-replicating organism on this planet. D) No one has ever created life from non-life, and E) Life was present on this planet from the very beginning.

The first Earthlings likely included archae, blue-green algae (cyanobacteria), bacteria, viruses, and possibly single celled eukaryotes. Some of these creatures may have journeyed through space as spores, yet others may have dwelled and reproduced within planetary debris, and some may have lived beneath the surface of this planet before it was captured by this solar system (Joseph and Schild 2010b).

Many species of bacteria form spores (Marquis and Shin 2006) and some survive in a state of suspended animation for hundreds of millions of years (Satterfield et al. 2005; Vreeland et al. 2000). Single celled eukaryotic organisms, including yeast and fungi (Botts et al., 2009), also produce spores, often for reproductive purposes, but also in response to adverse, life threatening conditions. Therefore, it is possible that some simple eukaryotic organisms, and their descendants, along with trillions of other microbes, may have survived the destruction of the parent star system and the ejection of this planet during that sun's red giant phase and prior to supernova. If so, this would explain the presence of microfossils resembling yeast cells and fungi, discovered in 3.8 BY old quartz (Pflug 1978) and for the evidence of biological activity in this planet's oldest rocks (Nemchin et al. 2008; O'Neil et al. 2008).

This proposition is in fact supported by the discovery of microfossils recovered from the Orgeuil, Ivuna, Murchison, Efremovka and other meteorites (Claus & Nagy 1961; Hoover 1984, 1997; Nagy et al. 1962; Nagy et al. 1963a,b,c; Zhmur and Gerasimenko 1999; Zhmur et al. 1997), each of which may have originated on ancient planets which predate the origin of this solar system. Therefore, it appears that simple eukaryotic and prokaryotic organisms may have been deposited on this planet soon after it became a member of this solar system.

If single celled eukaryotes also arrived on Earth encased within debris, or if they emerged from deep beneath the surface of this planet, they may have phagatocized surface dwelling archae and bacteria and incorporated their genes. Or they may have been infiltrated by parasitic prokaryotes which donated genes to the eukaryotic genome, thereby triggering multi-cellularity and compartmentalization (Joseph 2009b). A third possbility is that the first Earthly eukaryotic cells were created by the genetic fusion of bacteria and archae coupled with the injection of viral genes. Each of these scenarios, and variations therefore, leads to the same result: genes donated by archae, bacteria and viruses, in combination with biologically engineered environmental influences, gave rise to the first multicellular eukaryotes, which 4 billion years later, would eventually evolve into humans.

Evolution is not random. The step-wise, sometimes leaping progression leading from simple to complex species to the metamorphosis of humans was genetically regulated by complex genetic-environmental interactions resulting in the expression of precoded genetic traits encoded into genes acquired on other, more ancient worlds (Joseph 2000). In fact, many genes including those of the human genome, can be traced to viruses and backward in time to the "last common ancestors" of eukaryotes as well as to archae and bacteria. However, these genes did not originate in an Earthly-organic soup or deep sea thermal vent. These genes were inherited and obtained from microbial species whose ancestors arrived in debris jettisoned from other planets, and from species which already dwelled deep beneath this world before it became Earth. As most scientists agree that modern life can trace its origins to the first Earthlings, then we can conclude that all life on Earth has a genetic ancestry which leads to other planets.

Microbes continually exchange genes, including genes they have acquired from other species, such that trillions of copies are collectively maintained in the genetic libraries of innumerable single-celled creatures and their viral associates. Horizontal gene transfer has likely taken place on innumerable planets and wherever life comes in contact with life or with viruses. Therefore, when microbes are jettisoned into space, they carry with them vast genetic libraries, with different microbes and innumerable viruses maintaining different genetic luggage (Joseph 2000, 2009b; Joseph and Schild 2010b). In their role as intergalactic genetic messengers, and via mechanisms of panspermia, this is the equivalent of dispersing trillions of genes via innumerable microbes and viruses, thus insuring that at least some of this genetic cargo and these genetic libraries are delivered to other worlds. Therefore, once these microbes and viruses took root on Earth, they began exchanging the genes acquired form other worlds, and which became part of the genomes of Earthly multi-cellular eukaryotes.

Eukaryotes received from prokaryotes a variety of genes, proteins and transcription enzymes which have played a major role in genetic continuity, gene duplication, and synthesis and transcription of long DNA molecules, thus shaping and guiding what has been called evolution. These elements and genetic mechanisms, including RNA polymerase, replicative DNA polymerase, introns and transposable elements, enabled genes and entire genomes to be duplicated. Regulatory genes inserted by viruses and prokaryotes, also guaranteed genetic linkage between genes, insured accurate replication and transmission of genetic information following gene or whole genome duplication (Harris et al., 2003) over billions of years of time. Because individual silent genes as well as the entire genome can be duplicated and then transmitted to subsequent species, once these genes were activated by biologically induced changes in the biosphere, this gave rise to preprogrammed diversity and allowed the same trait or characteristic to evolve, seemingly independently, in numerous divergent species, almost simultaneously, as took place during the Cambrian Explosion 540 bya.

Via these genetic mechanisms, silent genes, gene sequence, and related elements that encode for advanced characteristic, such as the heart, eyes, and brain, could be duplicated and passed down for billions of years to subsequent species which would maintain these genes even without expressing them and without losing genetic information. However, over billions of years of time, in response to major alterations in the environment, after undergoing repeated duplications, and in reaction to environmental, regulatory, and other genetic signals, the traits coded by these silent genes were expressed. Ultimately this led to increasing multicellularity, then vertebrate complexity and the rapid evolution of new species including humans.

2. THE ORIGIN OF EARTHLY LIFE

Life had taken root on the surface of this planet by 4.2 BYA, a time when Earth was undergoing continual pummeling from rogue planets and planetary debris and remnants produced by the exploding parent star and its planetary system (Joseph 2009a). The nature of the first and earliest surface-dwelling Earthlings can only be inferred indirectly based on the residue of photosynthesis, oxygen secretion, carbon isotopes, the structure of banded iron formations and high concentrations of carbon 12, or �light carbon;� all of which are typically associated with microbial life (Manning et al. 2006; Mojzsis et al. 1996; Nemchin et al. 2008; O'Neil et al. 2008; Rosing, 1999, Rosing and Frei, 2004; Schoenberg et al. 2002). Some of those microbes may have included single celled eukaryotes, as microfossils resembling yeast cells and fungi were discovered in 3.8 BY old quartz (Pflug 1978). Thus eukaryotes such as fungi and yeast cells were already proliferating upon the surface by 3.8 BYA, and they were no doubt accompanied by bacteria and archae--and this has been demonstrated by geo-physical and biochemical analysis indicating evidence of biological activity from 4.2 to 3.8 bya (Manning et al. 2006; Mojzsis et al. 1996; Nemchin et al. 2008; O'Neil et al. 2008; Rosing, 1999, Rosing and Frei, 2004; Schoenberg et al. 2002).

3. THE FIRST EUKARYOTES

Archae, bacteria, and viruses can survive in almost any extreme environment, and bacteria and viruses are also preadapted to surviving the harsh conditions of space. Prokaryotes and viruses are ideally suited for traveling between planets and seeding worlds with life. Microfossils resembling archae, bacteria, and viruses have in fact been discovered in meteors which predate the origin of this solar system and which may have originated on other planets. As there is no evidence that Earthly life can be produced from non-life, then the only scientific explanation for the origin of Earthly life is panspermia, i.e. life was deposited on this planet contained in comets, asteroids and planetary debris (Hoyle and Wickramasinghe, 1984, 2000; Joseph 2000, 2009a,b).

As detailed by Joseph and Schild (2010a), life could never have begun on this planet, but was most likely first fashioned in a nebular cloud, long before Earth or this solar system were formed. Life may had more than one origin (Joseph 2010).

Once life became life then through mechanisms of panspermia, its descendants were cast from planet to planet, from solar system to solar system, and from galaxy to galaxy, and over eons of time. Life evolved, diversified, became increasingly complex, then sentient and intelligent on innumerable worlds. And just as takes place on this planet, genes were exchanged between species through horizontal gene transfer. Thus, bacteria, archae, and viruses began acquiring vast genetic libraries long before this planet was formed, and eventually the descendants of these creatures, accompanied by their viral luggage, arrived on Earth (Joseph and Schild 2010b).

Woese (2004) has proposed that these initial bacteria, archaea and eukaryotes may have lived together and repeatedly swapped and shared genes. "Eventually this collection of eclectic and changeable cells coalesced into the three basic domains known today. These domains become recognisable because much (though by no means all) of the gene transfer that occurs these days goes on within domains" (Woese, 2004).

However, another important factor effecting eukaryotic evolution was the injection of viral genes. On the modern Earth bacteria are everywhere and are generally surrounded and outnumbered by viruses at a 1 to 10 and 1 to 100 ratio. Viruses often serve as genetic libraries, containing vast number of genes (Claverie 2005) which are often selectively provided to bacteria such as in times of stress, and which enhance bacteria functioning and even promote bacterial evolution (Lindell et al., 2004; Sullivan et al., 2005, 2006; Williamson et al., 2008; Zeidner et al., 2005). Viruses also provide genes to the eukaryotic genome (Conley et al., 1998; Medstrand et al., 2002) and some of these genes appear to have been involved in triggering evolutionary transitions such as between monkeys and apes and apes and hominids (L�pez-S�nchez et al., 2005; Romano et al., 2007).

Evolution has been likened to metamorphosis and embryogenesis (Joseph 2000, 2009a,b). And just as embryological development and metamorphosis are under genetic-environmental control, what has been called a random "evolution" is also regulated by genes and the changing environment. And just as life comes from life, these genes were also inherited from other life forms, copies of which were obtained from creatures which long ago lived on other planets and which were deposited on Earth, like so many seeds, contained within the genomes of prokaryotes and viruses. And just as apple seeds contain the genetic instructions for the generation of apple trees, these extraterrestrial genetic seeds contained the genetic instructions for the tree of life, the replication of creatures which dwelled on other planets. However, rather than a single season, or a few years, it may take billions of years to genetically engineer a suitable planet and to grow complex species such as humans. Thus, in this regard, viruses, prokarotes and eukaryotes can be viewed as a genetic superorganism which interacts to promote evolution and metmorphosis.

Therefore, it appears that hundreds of millions of years after arriving on Earth, archae, bacteria, and virus may have joined together, combining their genomes, or transferred genes into a single celled eukaryote, and in so doing, created the first multi-cellular eukaryotes, which, nearly 4 billion years later, would give rise to humans.

4. ARCHAE VS BACTERIA: GENE TRANSFER

Numerous species of bacteria act as endosymbionts or endoparasites (Dyall et al., 2004; Poole and Penny 2007). Viruses are parasitic by nature. Archaea do not generally serve in this capacity--though there are exceptions as archae and associated viruses have been found in the human gut. Bacteria and viruses are completely distinct and even within species there are significant differences (Nakabachi et al., 2006; Ranea et al., 2005; Schulz and Jorgensen 2001; Schneiker et al., 2007) .

Considered in the broadest terms, archaea are highly distinct from bacteria, particularly in regard to the size of their genomes and cell membranes. For example, archaean membranes are made of ether lipids where as bacterial cell membranes are created from phosphoglycerides with ester bonds (De Rosa et al., 1986). Like bacteria, archae can live in the most extreme environments (Kimura et al, 2006, 2007; Leininger et al., 2006; Robertson et al., 2005). However, whereas bacteria are usually (but not always, e.g. Leininger et al., 2006) the most common form of life in the soil, archaeota are the most common form of life in the ocean, dominating ecosystems below 150 m in depth (Karner et al., 2001; Robertson et al., 2005).

The genomes of archae are rather uniform and compact in size ranging from 0.5 Mb in the parasite Nanoarchaeum equitans (Waters et al., 2003) to 5.5 Mb in Methanosarcina barkeri (Maeder et al., 2006).

Bacterial genomes can vary by two orders of magnitudes, from 180 kb in an intracellular symbiont, Carsonella rudii (Nakabachi et al., 2006), to 13 Mb in Sorangium cellulosum which dwells in soil (Schneiker et al., 2007). Although there are bacterial genomes of intermediate size, the vast majority of bacteria so far sequenced show a clear-cut bimodal distribution of genomes; i.e. large vs small, suggesting the existence of two distinct classes of bacteria: those with �small� genomes (Ranea et al., 2005) with the highest peak at 2 Mb and those with "large" genomes at about 5 Mb (Schulz and Jorgensen 2001).

By contrast, eukaryotic genomes range wildly in size and are generally several magnitudes larger than those of prokaryotes. However, the genomes of some eukaryotic species, such as microsporidian Encephalitozoon cuniculi (Katinka et al., 2001) are substantially smaller than many bacteria and archaeal genomes. Encephalitozoon cuniculi is also a parasite and may serve as a genetic messenger.

Likewise, those bacteria and archae with the smallest genomes share a significant behavioral feature with Encephalitozoon cuniculi: they too are parasites and they prey upon other prokaryotes as well as eukaryotes (Waters et al., 2003; Huber et al., 2002). It is these parasitic behaviors which may explain their small genomes, and the presence of prokaryotic genes in the eukaryotic genome. These prokaryotes likely donate their genes after invasion or they form parasitic relations with those eukaryotes who already maintain these genes in their genomes. Moreover, many species of parasitic bacteria/archae have taken up residence inside a eukaryotic host after which they continued to transfer and donate genes (Dyall et al., 2004; Margulis et al., 1997).

Once donated many of these genes were not replaced due to genetic mechanisms which ensure that they will only become activated in targeted eukaryotic species

For example, prokaryotes with the smallest genomes, i.e. parasitic and symbiotic bacteria and archaeal parasites (e.g., N. equitans) no longer encode or express a variety of protein regulators, indicating the responsible genes have been transferred to the genome of the eukaryotic host. With the donation of these regulatory genes, the genomes of these parasitic and symbiotic prokaryotes decreased in size.

Hundreds of specialized prokaryotic genes have been donated to the genomes of their hosts, possibly by horizontal gene transfer (Yutin et al., 2008) and were then preserved, unchanged, often in the same position even after hundreds of millions and, perhaps, even after billions of years of evolution. Some of these donated genes appear to to be responsible for the metamorphosis of mitochondria which also donated genes to the eukarayote genome (Margulis et al., 1997).

These prokaryotic genes and bacteria/archae symbionts, enabled eukaryotes to become increasingly complex and to colonize and conquer new environments which were being genetically engineered by prokaryotic genes. For example, genes which are responsible for photosynthesis altered the environment via the liberation, secretion, and synthesis of a variety of chemicals and enzymes including oxygen (Buick 1992, 2008; Falkowski and Godfrey 2008; Holland 2006; Olson 2006; Williams and Fra�sto da Silva 2006). Much of this photosynthesizing activity was carried out by cyanobacteria (blue green algae). However, as has been demonstrated (Lindell et al., 2004; Sullivan et al., 2005, 2006; Williams et al., 2008), viruses provided cyanobacteria with genes which enhanced their ability to engage in photosynthesis, thus releasing oxygen which acted on gene selection. Therefore, the genetic activities of viruses and prokaryotes activated genes within the eukaryotic genome which had been contributed by bacteria, archae, and viruses, giving rise to new traits and new species perfectly adapted for a world that had been prepared for them.

5. VIRUSES AND GENE DONATION

Viruses serve as vast storehouses of genetic information and they remain viable even after these genes are transmitted to other species. Viruses act as gene conservatories and can increase the gene pool within the genome of a host (Sullivan et al., 2006; Zeidner et al., 2005). Some of these genes are transferred to other hosts only during times of environmental stress which threaten potential hosts. After these genes are transferred and when activated they benefit not only the host but innumerable life forms. For example, viruses store genes which code for photosynthesis (Lindell et al., 2004; Sullivan et al., 2005, 2006) and the conversion of light to energy (Williams et al., 2008). However, these genes provide no direct benefit to the virus and are transferred to the genomes of photosynthesizing organisms, such as cyanobacteria, during periods of reduced sunlight and when there are insufficient nutrients to maintain energy output (Sullivan et al., 2006). When cynobacteria receive these genes they are able to maintain or even increase photosynthetic activity during these periods of environmental stress, which means oxygen continues to be excreted into the atmosphere even after prolonged periods of decreased sunlight or nutritional depletion. The beneficiaries are all oxygen breathing creatures, and their genes. When sunlight or energy supplies increase, these genes are no longer necessary and are transferred back to the virus genome for storage (Lindell et al., 2004; Sullivan et al., 2005, 2006). Viruses maintain vast genetic libraries and the function and purpose of most of these genes are unknown.

When a virus invades a single celled organism, it may donate its genes which become incorporated into the genome of the host. When viruses invade eukaryotes, they may sicken the host and eventually die. However, virus induced illness appears to be a genetic programming error, due to a mis match between virus and host.

Often viral genes may be inserted into the genome of the host germline and are then passed on to offspring and subsequent species. These later type of viruses are called endogenous retrovirus (ERV) and they have had a direct impact on evolution leading to humans. In fact, human evolution has been shaped by successive waves of viral invasion (Sverdlov, 2000).

Endogenous retroviruses can alter host gene function and genome structure and the evolution of eukaryotic hosts. For example, in mammals, including humans, ERVs play an active role in placental, embryonic, and brain development (Anderson et al., 2002; Patzke et al., 2002 ; Wang-Johanning et al., 2001, 2003). Although viruses are often associated with disease, ERVs often provide substantial benefits to the host and are often subverted by the host for its benefit (Parseval and Heidmann 2005; Lorenc and Makalowski. 2003; Miller et al., 1999). For example, ERVs are responsible for the generation of proteins involved in the formation of placenta (Mi et al., 2000; Blond et al., 2000). ERVs promote cell fusion (Mi et al. 2000, Blaise et al. 2003) and provide a protective function, allowing for nutrients to pass from mother to fetus while simultaneously protecting the fetus against infection or rejection by the mother's immune system (Ponferrada et al., 2003; Prudhomme et al., 2005). ERVs are also highly expressed in many human fetal tissues including heart, liver, adrenal cortex, kidney and the central nervous system (Anderson et al., 1996, 2002).

ERVs are very active in the human genome (Lower et al., 1993; Medstrand and Mager 1998). They regulate human gene expression (Jordan et al., 2003; van de Lagemaat et al., 2003) and contribute promoter sequences that can initiate transcription of adjacent human genes (Conley et al., 2008). ERV-derived promoters have been found in roughly a quarter of all the human promoter regions so far examined.

There is nothing random about these viral-host interactions. Nor can they be explained by Darwin's theory of evolution or Darwinian notions of natural selection. Rather, these collaborative interactions are purposeful, highly coordinated, and under precise genetic, regulatory control.

Eukaryotic evolution, in general, has been impacted by repeated episodes of viral invasion and the insertion of viral genes into the host genome and which have conferred functional advantages to the host. Tens of thousands of viral genes exert regulatory control over gene duplication, and mediate gene and genome rearrangement, transduction and the silencing vs activation of genes (Crombach and Hogeweg 2007; John and Miklos 1988). Further once inserted, these viral genes can rapidly replicate and increase in number (Doolittle and Sapienza 1980; Tsitrone et al., 1999). They can also insert themselves into a variety of locations within the genome where they may promote gene expression or duplication; and this has been shown to be true even in the human genome. These ERV sequences, such as promoters, enhancers, and silencers determine when and which genes should be turned on or off and play important roles in the evolution of new species and in fetal and brain development.

ERVs have invaded the germ cell lines of all species of vertebrate. Once incorporated into the genome, they replicate in Mendelian fashion, and are transmitted via the germline as an integral part of the sexual reproduction of the host. However, genomes and germlines of subsequent species may also be invaded. It is because of repeated viral invasion and viral gene duplication, and the role these viral genes play in host gene replication, that the so many eukaryotic genomes have become enormous in size.

Retroelements encompass 42.2% of the human genome and almost half of the mammalian genome (Deininger and Batzer 2002; van de Lagemaat et al. 2003). The human genome contains 200 000 copies of endogenous retroviruses grouped in three classes (Lander et al. 2001), which have been introduced through at least 31 infection events (Belshaw et al. 2005). Coupled with the 158,000 mammalian retrotransposons inherited from common ancestors, ERVs make up 8% of the human genome (IHGSC 2001). Retroviral sequences encode tens-of-thousands of active promoters and regulate human transcription on a large scale (Conley et al., 2008). However, these percentages are only gross underestimates.

Endogenous retroviruses show a significant tendency to recombine thereby creating a variety of different recombination products. When a retrovirus reproduces, identical copies of viral gene sequences are created on either side of the retroviral element. When two different proviruses combine this can lead to substantial deletions or rearrangements of cellular DNA (Sun, et al. 2000) resulting in a high frequency of gene conversion events (Johnson and Coffin 1999). However, because these retrogenes can rapidly reproduce, recombine, and then spread to new positions, the oldest insertions are impossible to recognize as viral genes (Eickbush and Jamburuthugoda 2008), even in the human genome, and may be misidentified as bona fide human genes (Parseval and Heidmann 2005).

Human endogenous retroviruses, therefore, have induced large-scale deletions, duplications and chromosome reshuffling over the course of human genomic evolution (Hughes and Coffin 2001). This has been accomplished by enhancing transcription levels, altering tissue specificity of gene expression, or creating new gene products with modified functions. Hence, viral elements have played a major role in mammalian-primate-human evolution and they have interacted with genes donated to the eukaryotic genome by prokaryotes.

5. CONSERVED GENES & GENE EXPRESSION

The number of eukaryotic genes which were or have been donated by prokaryotes or viruses is unknown, though ultimately it may be that all eukaryote genes are derived from prokaryotes and viruses.

Thousands of orthologous genes and hundreds of conserved genes can be traced back to the last common ancestor for eukaryotes (Snel et al., 2002; Mirkin et al., 2003; Kunin and Ouzounis 2003; Koonin 2003; Mushegian 2008; Bejerano et al., 2004). Almost all underwent duplication at the onset of eukaryotic evolution (Makarova et al., 2005), which, when coupled with gene deletions, exon shuffling, and the transposing of genes to other regions of the genome, obscured and erased considerable evidence of their prokaryotic origins.

These genes then continued to undergo repeated episodes of single gene and whole genome duplication such that the eukaryotic genome increased in size. However, these duplications continued to be coupled with gene deletions and transpositions further obscuring their original relationship with prokaryotes and viruses.

Almost all of the genes donated by prokaryotes, including many inserted by viruses, have performed crucial functions that have guided the trajectory of evolution. These donated genetic elements include regulatory genes and genes controlling core cellular activities and the capacity to make duplicates of individual genes and the entire genome.

Genome sequencing has revealed an extensive conservation of the same repertoire of genes coding for core cellular functions in the genomes of prokaryotes and eukaryotes (Koonin et al., 2004; Koonin and Wolf 2008). A core set of approximately 70 genes contributed by archae and bacteria have been identified. These have been conserved and passed down, without deletion, for billions of years, and make up around between 1% to 10% of the genes in the genomes of all multicellular life (Koonin 2003; Koonin and Wolf, 2008; Harris et al., 2003; Charlebois and Doolittle 2004).

These conserved genes, proteins, and gene sequences (Koonin 2002, 2003, 2009b), include those governing translation, the core transcription systems, and several central metabolic pathways, such as those for purine and pyrimidine nucleotide biosynthesis. Moreover, protein sequence conservation extends from mammals to bacteria thus demonstrating their great antiquity (Dayhoff et al., 1974; Eck and Dayhoff 1966; Dayhoff et al., 1983).

Between 2150 to 4137 orthologous gene sets are highly conserved and can be traced back to the last common ancestor for eukaryotes (Makarova et al., 2005). And often these orthologs express or perform the same function regardless of species. In the human genome, these ultraconserved elements often overlap introns or genes involved in the regulation of gene transcription and expression. Many regulatory genes, including introns, orginated in the viral genome.

6. CONSERVATION OF VIRAL INTRONS

Introns are directly relevant to the regulation of gene function and expression and RNA processing and have also been highly conserved and preserved often in the same places in the genome, over the course of evolution, be it the genes of Drosophila melanogaster (the fruit fly), Caenorhabditis elegans (nematode), mice, or humans (De Souza et al., 1996; Federov et al., 2002). Thus the positions of a large number of introns are conserved between plants and vertebrates (Fedorov, et al., 2002; Rogozin et al., 2003; Roy and Gilbert 2006) and between mammals and "living fossils" such as as Trichoplax and the sea anemone (Putnam et al., 2007; Srivastava et al., 2008); species which diverged over a billion years ago. This includes the positions of a large fraction of introns with 25�30% conservation in orthologs from plants and chordates (Fedorov et al., 2002; Rogozin et al., 2003; Roy and Gilbert 2006). This extreme conservation and preservation of their positions within genes and the genome, attests to their importance in regulating and coordinating the evolution and metamorphosis of numerous species.

Introns are of particular importance in regulating gene expression (Brinster et al., 1988; Buchman and Berg, 1988; Collis et al., 1990; Lai, et al., 1998; Noe et al., 2003) and play a major role in the regulation of gene transcription and the creation of new genes from old genes. If different "starter" or "stop" introns are activated this results in different segments or sequence lengths becoming expressed, thereby producing a different protein product (Belfort, 1991, 1993; Breathnach et al., 1978; Breibart et al., 1985; Leff et al., 1986) which can give rise to different tissues and organs. Hence, variation and diversity can be differentially induced if different "starter" or promoter introns are activated.

Some introns are found within or in association with ribosomes (D�rrenberger and Rochaix 1991; Jackson et al., 2002; Toro et al., 2007; Yoshihama et al., 2007). The functional part of the ribosome is fundamentally a ribozyme, the molecular machine that translates the RNA copies of exons into proteins (Cech 2000). Thus introns, in association with ribosomes play a major role in translation, transcription and protein synthesis. Ribozymes are also able to splice themselves and other introns out of the original transcript created by these RNA molecules (Jackson et al., 2002). Ribozymes can also be found in the intron of RNA transcripts, which had been removed from the gene sequence being processed and expressed.

Mitochondrial ribosomes and a significant number of introns are considered to be of bacterial origin (Kenmochi et al., 2001); a product of endosymbiosis (Dyall et al., 2004; O'Brien 2002). Yet other introns were inserted by viruses. Even those inserted into the eukaryotic genome by bacteria and archae, may have been stored in the viral genome.

Ribosomal introns and protein sequences which circulate in the cytoplasm appear to have originated in the archae genome, and were later donated to eukaryotes, as there is a specific affinity between eukaryotic genes and their orthologs from archae (Lake et al. 1984; Lake 1988; 1998; Rivera and Lake 1992 Rivera and Lake 2004 Vishwanath et al. 2004). Archae and bacteria, therefore, were a major source of introns and ribosomes, with viruses also contributing introns, transposable elements, and other regulatory genes.

Viruses act as gene depositories and can donate regulatory elements to prokaryotes who in turn may horizontally transfer these genetic elements to eukaryotes. Viruses can also directly insert regulatory elements into the eukaryotic genome, including the genome of humans. For example, group II introns and ribozymes which are derived from viruses are found in the genomes of archae, bacteria, and eukaryotes (Dai and Zimmerly 2003; Dai et al., 2003), and retroviruses have continually inserted genes and introns into the primate lineage leading to humans (IHGSC 2001; L�pez-S�nchez et al., 2005; Medstrand et al., 2002; Romano et al., 2007). This suggests that viruses may have served as a genetic storehouse for introns and ribozymes which were subsequently transferred to prokaryotes and eukaryotes, and which the directed and guided the trajectory of what we call evolution.

In bacteria, approximately 35% of group II introns are linked to plasmids and are thus highly mobile (Dai et al., 2003; Klein and Dunny 2002) and can exit the bacteria genome and insert themselves into the genomes of eukaryotes, prokaryotes, and possibly back into the viral genome. Plasmids and viruses share many characteristics as both serve as mobile carriers of packets of DNA.

Group II introns are highly mobile retroelements (Belfort et al., 2002. Lambowitz et al., 1999; Lambowitz and Zimmerly 2004) and include retrotransposons (Beauregard, et al., 2008) and are progenitors of nuclear spliceosomal introns (Cavalier-Smith 1991; Jacquier 1990; Sharp 1991). Retroelements have as their source, retro-viruses. These retroelements can splice together exons (Bonen and Vogel 2001; Michel and Ferat 1995), thereby creating genes from genes. Spliceosomes and spliceosomal introns are responsible for splicing out introns and transposable elements, and insuring that the genetic sequences in introns are not translated into proteins. Thus, they regulate gene expression and help guarantee that only designated exons are translated and transcribed (Roy and Gilbert, 2006).

Spiceosomal introns and are found in the nuclear genes of higher eukaryotes including humans (Doolittle 1978; Gilbert 1978; Mattick 1994; Deutsch and Long 1999). Again, however, they appear to have originated in viruses and prokaryotes and may have been first transferred to the eukaryotic genome billions of years ago and then periodically thereafter.

Thus, genes involved in transcription regulation and which were donated by viruses and prokaryotes to eukaryotes interact with and overlap genes and introns also contributed by viruses and prokarayotes to eukaryotes. These same genes have also been repeatedly duplicated and dispersed to a wide range of divergent species often in silent form. There is nothing random about these interactions as they are under precise genetic regulatory control. When activated these genes have given rise to identical or similar evolutionarily advanced characteristics in numerous species nearly simultaneously, such as the photoreceptors of the eye and the nerves and neurotransmitters of the brain.

Viral genes which have become part of the eukaryotic genome are involved in the generation and metabolism of nerve tissues and the brain (Andersson et al., 2002; Conley et al., 2008; Seifarth et al., 2005) whereas yet others code for photoadaptation and the conversion of light to energy (Williams et al., 2008). Thus, viruses have also provided eukaryotes with the genes necessary to evolve highly complex perceptual and intellectual organs such as the eye and brain.

It is important to emphasize that these genes existed long before the evolution of these tissues and organs and were inherited in silent form from ancestral species which did not possess eyes, brains, or bones. It is impossible to believe that so many creatures randomly evolved the same genes, which remained silent, only to be expressed almost simultaneously in later emerging species. Genes coding for eyes and brain had to have been obtained via horizontal gene transfer from creatures which possessed eyes and brains; beings with lived and evolved on other planets.

7. GENE CONSERVATION: THE EYE OF THE BEHOLDER

It has been claimed that the chief components of the eye, such as photoreceptors must have evolved de novo in 65 different species, independently and randomly according to Darwinian principles (Salvini-Plawen & Mayr 1977). However, these genes did not randomly evolve, they were inherited from a variety of species, albeit in silent form and then passed down to numerous species only to be activated by environmental and regulatory signals. For example, genes involved in eye development, known as Pax, "Pax-6" and opsin in vertebrates and "eyeless" in fruit flies, are homologous between diverse phyla (Quiring et al., 1994; Gehring & Ikeo 1999). However, Pax genes ("Pax-6") have been found in the genomes of ancient species such as the sea urchin and trichoplax, both of which have no eyes and cannot see (Sodergren et al., 2007; Callaerts et al. 1997; Hadrys et al., 2005).

Pax-6 serves as a master regulator of a network of genes that can give rise to a variety of different types of eyes that utilize the same visual pigment genes. That is, Pax-6 appears to act on different genes to produce the different structures on which the pigment cells are mounted in different creatures giving rise to a variety of eyes (Sheng et al., 1997; Gehring and Ikeo, 1999; Davidson, 2001). Pax 6 proteins are master regulators, and highly conserved, and show an 90-90% identity between vertebrate and invetebrates (e.g. squid) as well as insects (Drosophila) and marine worms (Tomarev, 1997).

According to the Darwinian apologists, the independent evolution of the same structures and the same genes are due to "nature arriving at the same solution" merely by chance. However, genes do not evolve de novo or ex nihilo; they are transferred from another species, inherited from an ancestral species, or they are produced through recycling by exon shuffling, single gene and whole genome duplication, and numerous other replicative mechanisms.

As the common ancestors for vertebrates and invetebrates diverged between 600 mya to 1.6 bya (Ayala et al., 1998; Wray et al., 1996; Gu, 1998; Cutler, 2000), this is an indication of the great antiquity of Pax genes which can be traced to ancestral species who had no eyes and were unable to see. Those ancestors could include prokaryotes and possibly viruses. Consider, for example, vitamin-A-related chromophores in the visual pigment and which is the single most prerequisite for vision in the vertebrate or invertebrate genome. Vitamin-A-related chromophores are also found in bacteria as well as algae (Seki and Vogt 1998; von Lintig and Vogt 2004).

These highly conserved genes, albeit in silent form, are present in the genomes of the most ancient species on this planet, i.e. prokaryotes; species which inserted genes into the genomes of eukaryotes. These ancient genes were then passed down through numerous diverging ancestral species until activated in the period leading up to and including the Cambrian Explosion, such that thousands of species simultaneously evolved eyes around 540 mya. Over 1000 genes involved in visual functioning, including ancestral Pax-6 genes, were inherited and are homologous between phyla (Gehring and Ikeo, 1999; Quiring et al., 1994; Tomarev et al. 1997), and have been isolated from invertebrate and vertebrate species, including squid, flatworm, ribbonworm, ascidian, sea urchin, nematode, and fruit flies (Callaerts et. al., 1997; Tomarev, 1997).

Be it vertebrate, flatworm or insect, and in spite of the large differences in eye morphology and mode of development (Gehring 1996), the same genes and same gene products related to the visual system are under the same genetic control (Quiring et al., 1994). Thus, regardless of species some parts of the eyes are homologous because they are coded by the same genes and the same proteins. It is not rational to assume these genes just randomly evolved in so many different species and that master regulatory proteins were conserved just by chance.

Between 70% to 80% of these genes have been evolutionary conserved and are found in the genomes of mammals, squid, octopus, flatworm, ribbonworm, ascidian, and nematode mosquitos, flies, tunicates, and vertebrate genomes including humans (Ogura et al., 2004). The common ancestors for these species diverged anywhere from 1.2 bya to 830 million years ago (e.g., Wray et al., 1996; Peterson et al., 2004, Nei et al., 2001; Gu 1998). As there is no evidence for visual functioning in any creature before 550 mya, these genes were therefore inherited, in silent form, from ancestral species which could not see. The only rational explanation for the existence of these genes is that they were obtained by viruses and prokaryotes through horizontal gene transfer, from complex species with eyes, who long ago evolved on other planets.

8. CONSERVED GENES, DARWINISM, AND VIABILITY

Genes that are highly conserved over the course of eukaryotic evolution not only remain in the same location within diverse eukaryotic genomes, but accumulate fewer substitutions in their protein sequences. Therefore the conservation of a gene and regulatory elements including introns, and the fact they are passed down vertically to subsequent species and are maintained unchanged in the same position, indicates these processes are controlled by precise genetic mechanisms. Further, many of these genes are passed down in silent form, and thus could not have been naturally selected according to Darinwian dogma as they provided no adaptive value for these ancestral species, but only for future species which had not yet evolved.

Then there is the fact that many of these conserved genes, once expressed by introns, play identical roles, almost regardless of species, and contribute to the progression known as "evolution." The conservation of these genes has more to do with the future of evolution rather than the survival of the species possessing that gene. Darwinian concepts of "Survival of the fit" or "natural selection" explain nothing. In fact, some highly conserved genes can be removed (knocked out) of various genomes without having any noticeable impact on the viability of the organism or its ability to function (Koonin 2000). Hundreds of genes have been knocked out, or stripped from the genomes of various species which remained viable (Glass et al., 2006; Koonin 2000).

Mycoplasma genitalium, for example, has one of the smallest genome of any organism but remained viable even after 100 of its 482 genes were removed (Glass et al., 2006). Further, 28% of the minimal set of its genes coded for unknown functions (Glass et al., 2006). Moreover, 80 genes of the original minimal gene set were represented by orthologs in all forms of life and many of these coded for unknown functions (Koonin 2000).

Mycoplasma genitalium

Therefore, not all highly conserved genes are related to the viability or "fitness" of the organism. Nor are they conserved because of "natural selection." Many were passed on in silent form, and serve to facilitate the evolution of specific organs and tissues when they were activated in response to specific biologically engineered environmental conditions. Therefore, highly conserved genes whose functions are unknown and which still have not yet been expressed, may continue to be held in reserve, in storage, and transmitted from generation to generation until they activated at some future date, thereby giving rise to a species which has never before evolved on this planet.

9. VIRUSES AND GENOME DUPLICATION

Many of the genes within the eukaryotic genome appear to have originated prokaryotes and were then stored in viruses which then inserted these genes into specific eukaryotic hosts. For example, numerous homologous relationships have been identified among the proteins of crenarchaeal viruses and those from prokaryotic and eukaryotic cells, including DNA precursor metabolism enzymes, RNA modification enzymes, glycosylases transcription regulators, and ATPases implicated in viral DNA replication and packaging (Prangishvili et al., 2006). Some of these proteins were obtained from crenarchaeal hosts or bacteria and were then stored in the viral genome and then transfered from virus to eukaryote; which indicates the highly regulated interactions and various complex routes these genes may take (Prangishvili et al., 2006), i.e. from prokaryote to eukaryote, or from prokaryote to virus to yet other viruses, and then to eukaryote.

Species and their genes interact. Genes inserted by archae and bacteria into the eukaryotic genome may be regulated by genes inserted by viruses. These regulatory interactions require a precise "lock and key" fit, and are not random but are genetically coordinated and under precise genetic control. Viruses in fact, target specific hosts, and some viruses hold these genes in reserve until that host evolves.

Broadly considered from the genomic perspective, there are two types of viruses, those with an RNA genome, and those whose genome consists of DNA. In order to replicate, DNA viruses are completely dependent on the host cell's DNA and RNA synthesising and processing machinery. By contrast, RNA viruses manufacture their own RNA replicase enzymes and can therefore replicate themselves by hijacking the host cell's RNA machinery within the cytoplasm. Viruses, therefore, insert genes or replicatory proteins and enzymes which control and guide gene replication and activation.

Retroviruses, however, do not merely attack host species in order to replicate, but to intwine their genes with the host genome. These viruses manufacture enzymes (reverse transcriptase), to reverse transcribe the host's RNA to create a complementary viral DNA which then becomes an integral part of the host genome. Numerous copies of this viral DNA are then replicated and then transmitted via the germline through daughter cells, to subsequent generations.

Autonomous retrotransposable elements, for example, make copies of themselves by releasing reverse transcriptase, which is an RNA-dependent DNA polymerase. This substance catalyzes reverse transcription of RNA transcripts into DNA, thus producing new copies of the retroelement and increasing their number by duplication. Retrotransposition is largely responsible for the proliferation of retroelements in many vertebrate genomes.

Therefore, viruses contain the genetic instructions necessary for duplicating individual genes. However, it is not just viral genes which may be duplicated, by host genes, including those originally inserted by archae and bacteria. In fact, viral genes can duplicate an entire genome.

After the RNA genome of an extracellular retrovirus is copied into DNA by virus-encoded reverse transcriptase it is then integrated into the nuclear DNA and thus the chromosome of the host cell via a viral enzyme integrase (Vogt 1997). Yet other retroviruses transpose via DNA excision and reintegration into the host genome. These are referred to as transposons. Integration is highly stable and, consequently, infection of germ line cells can lead to vertical transmission of retroviruses from parent to offspring as Mendelian alleles (Boeke and Stoye 1997). However, many of the viral-replicatory genes remain silent until their activation is triggered by specific genetic events and environmental signals. Yet others replicatory genes and proteins may be suppressed by these same signals. Via the turning on and off of genes, new species may be generated whereas others may become extinct.

Thus there are two classes of retroviruses based on their mechanism of mobilization: those that transpose via DNA excision and which are associated with transposons, and those involving an RNA intermediate and which are represented by retrotransposons and endogenous retroviruses (ERVs). These employ reverse transcriptase that copies the viral RNA template to its complementary DNA, which is then integrated into the chromosomes. The integrated DNA of a retrovirus is called a provirus. There they may remain, silent or active, until specific genetic and environmental signals triggers their activation or inhibition.

10. VIRUSES TARGET SPECIFIC HOSTS TO PROMOTE HOST EVOLUTION

ERVs are relics of ancient viral infection events in the germ line, followed by long-term vertical transmission through subsequent generations and species. Once embedded in the genome they can increase in copy number by means of active replication or by chromosomal duplication (Boeke and Stoye 1997). The latter property provides a means for retroviruses to colonize the germ line. Therefore, the progeny of the infected germ cell will inherit the provirus formed as an endogenous retrovirus (Boeke and Stoye 1997). However, because they can move about the genome, many of these ERVs are no longer recognizable as ERVs and become indistinguishable from other eukaryotic genetic elements.

A considerable proportion (~45%) of the primate genome consists of recognizable copies of mobile genetic elements (Landers et al., 2001). Retroelements constitute 90% of the ≈3 million transposable elements present in the human genome (Deininger and Batzer 2002). Further they play an activate role in evolutionary development. Great numbers of mobile elements, including retroelements, have been identified in the mRNAs of rapidly evolving mammalian genes. Transposable elements play a very activate role in the diversification and expansion of gene families, facilitating and even accelerating the speed of evolution.

Thus, be it RNA or DNA viruses, all are able to use the host's genetic endowment to create multiple copies of the virus genome. Because viruses have donated some of their own replicative machinery into the genomes of prokaryotes and eukaryotes, these viral genes also act to regulate host gene activity. These donated viral genes have in fact increased the size of the genome, and have played a major role in single gene and whole genome duplication. That is, just as viruses use the host genome to replicate the viral genome, this same genetic machinery, in response to specific biologically engineered environmental signals, replicates and duplicates individual host genes and even the entire genome of the host within which are embedded viral genes and other viral elements. In consequence, the host may evolve or at least acquire new or increased capacities enabling it to diversify and expand its host range and conquer additional niches and environments (Sullivan et al., 2005; Williams et al., 2008).

The defining feature of a virus is its ability to force the host genome to engage in replication while preserving the genes undergoing replication, i.e. those belonging to the viral genome and those donated by prokaryotes; genes which were likely obtained from an extraterrestrial host. Therefore, since viruses provided these regulatory genes during the early stages of eukaryogenesis, this would explain why the eukaryotic genome duplicated in size soon after it was fashioned, and why these particular genes, so important to gene replication, have been preserved and conserved; that is, for the purpose of additional genome duplications.

Most viruses target bacteria. However, in this capacity they also act as gene banks, transferring, receiving, and storing genes on behalf of trillions of species of bacteria; genes which could also be inserted into the eukaryote genome as specific eukarotic species evolve. Viruses acting as genetic storehouses, appear to have inserted the necessary or additional whole-genome-duplicating genes, periodically, over the course evolutionary history. However, if viruses first provided some of these genes to prokaryotes which transferred these genes to eukaryotes, or if they transferred these genes to eukaryotes, although highly conserved, the original ancestral viral origin has become increasingly obscured or erased.

It must be emphasized that the defining feature of the viruses including retroviruses, is that they are host-specific. For example, the human genome contain over 3 million viral genetic elements and around 200,000 viral genes (IHGSC 2001; Medstrand et al., 2002), many of which are still active (Conley et al., 1998; Medstrand and Mager, 1998). However, many of these viral elements were inserted before humans evolved at which point some became active and others silenced.

Since viral elements are host specific, and exist before the host evolves, and given the "lock and key" precision which is required for integration, this indicates that these viral elements, including the viral RNA or DNA genome are actually a template for DNA which must have been copied from another source identical to the host, but which lived before the target host evolved on this planet. Moreover, as these viral agents also existed prior to the evolution of their Earthly hosts, then they must have obtained these RNA DNA-templates from identical hosts who possessed an identical genome. In fact, the ease at insertion and integration, the fact that they viral gene-host genome are a perfect match, indicates that the original viral source for this RNA template of DNA was the DNA from an identical host which long ago lived on other planets. This explains the perfect virus-host match and the ease of viral DNA insertion, and the fact that these inserted genes often interact smoothly with a network of host genes, often to benefit the host. Moreover, these viral genes, once inserted act to purposefully increase the size of the genome and to promote and speed up speciation and evolution. These interactions can not possible be due to random chance, and when they are, the result is disease and death.

11. GENE REPLICATION, FUNCTIONAL PRESERVATION, & WHOLE GENOME DUPLICATION

Highly conserved regulatory genes and proteins donated by prokaryotes and viruses to the eukaryotic genome engage in coordinated, highly choreographed interactions through which genes, gene sequences, and proteins donated by prokaryotes, can be inhibited and suppressed even as they are repeatedly duplicated within the eukaryotic genome. Thus genes transferred to eukaryotes regulate gene expression, suppression, duplication, and preservation such that conserved genes and the functions they code for can be preserved even as they grew in number and are passed down to subsequent species over hundreds of millions and even billions of years; at which point they may be expressed in response to biologically engineered changes in the environment. Throughout the course of history these interactions have provided direct benefits to the host and have guided the pace and trajectory of evolution.

In this regard it must be emphasized that genes transferred to the eukaryote genome are regulated by genes which have been transferred to the eukaryote genome. For example, archae and bacteria contributed three subunits of the core DNA-dependent RNA polymerase (Iwabe et al. 1991; Klenk et al. 1993) and two enzymes of DNA metabolism, RecA and Pol1A to the eukaryotic genome (Eisen and Hanawalt 1999; Harris et al., 2003). These enzymes and the core RNA polymerase subunits serve many regulatory and replicative functions. Both RecA and Pol1A contribute to genetic continuity by gene conversion after recombination. They also insure the integrity and maintenance of genetic information as the lengths of DNA strands increase and the genome grows larger in size (Eisen and Hanawalt 1999). However, as most scientists agree that much if not all of the eukaryotic genome was originally fashioned through the combination of archae and bacterial genes, then again, this means that eukaryotes are acting as a host, or as a vehicle, through which these donated genes may interact such that only eukaryotes are effected.

The replicative DNA polymerase, DnaN (COG0592), and the gene for the �sliding clamp� were also donated. This gene and proteins are necessary for the high degree of processivity of DNA polymerase during replication (Kuriyan and O'Donnell 1993; Hingorani and O'Donnell 2000). This enables the accurate replication of linked genes and the preservation of the information they encode.

Many of the proteins that regulate eukaryotic signal transduction networks, including those involved in programmed cell death, are also derived from the prokaryotic genome (Aravind et al., 1999; Koonin and Aravind 2002; Bidle and Falkowski 2004). These signaling molecules are common in bacteria, cyanobacteria, and archae and include proteases from the AP-ATPase family. These proteases perform catalytic functions, and are found in the plant and animal genome (Koonin and Aravind 2002; Bidle and Falkowski 2004) and are utilized by mitochondria.

Replication is a universal feature of cellular organisms, and eukaryotes and prokaryotes share many genes and characteristics involved in replication, including the production of RNA primers, replication bidirectionality, strand synthesis, and the utilization of the same principal proteins involved in transcription and translation. That these genes were transferred from prokaryotes to eukaryotes (often with the aid of a viral intermediary) is demonstrated by their commonality.

Prokaryotic genes which guide replication and duplication contributed to the expanding size of the eukaryotic genome. Indeed, the number of signal transduction and regulatory proteins that are encoded parallel the increasing size of the genome. Thus, the larger the genome, the greater the number of genes dedicated to signal transduction (van Nimwegen 2003; Konstantinidis Tiedje 2004; Galperin 2005).

Some of these genes that can be traced to a common ancestor also perform functions that involve the transfer of genetic information (Harris et al., 2003). Some interact with ribosomes and those ribosomal RNA genes which play fundamenal roles in cellular functioning and DNA translation and transcription (Harris et al., 2003). Ribosome and ribosomal RNA genes were also likely transferred from prokaryotes to eukaryotes (Lake et al. 1984; Lake 1988; 1998; Rivera and Lake 1992; Rivera and Lake 2004; Vishwanath et al. 2004). However, ribozomes also have viruses as their source.

Thus, the ability to replicate and duplicate genes, and to transfer genes and to express these genes can be traced backwards in time to prokaryotes and viruses and thus to the direct descendants of the first creatures to arrive on Earth. Nor are these replicative actions somehow random processes. Instead, they are under regulatory control, performing essential functions related to the metamorphosis and evolution of future eukaryotic species; the metamorphosis and replication of life forms which lived on other planets.

12. GENE DUPLICATION AND EXPRESSION Viruses, archae, and bacteria were the dominant surface dwelling DNA-machines when this planet became Earth, and multi-cellular eukaryotes were fashioned by the combination of their genes. The eukaryotic gene pool steadily increased and the genome repeatedly doubled in size, replication being governed by genes and proteins donated by prokaryotes and viruses.

Gene and whole genome duplications (Dehal and Boore 2005; Lynch and Conery 2000; Lynch et al., 2001; McLysaght et al., 2002) does not necessarily result in gene expression. Instead, the original gene may have been repressed, and the copy suppressed as well. Thus pre-coded genetic instructions can be duplicated while repressed, and the silent genes in which this information is encoded, passed down through subsequent species. Then in response to activating signals from the environment, or within the genome, these genes may be freed from their repressive protein prisons, or they may undergo yet another duplicative event and these conserved genes or their newly copied twins may be expressed giving rise to advanced traits, organs and tissues which had never been seen before on Earth. Gene duplication is a major force in what has been called "evolution."

With each duplication, the original or duplicated genes may be freed from regulatory restraint. Genes are also deleted, and often the original prokaryotic insert may be removed or expelled from the genome; and this too may free up the copy from regulatory constraint thereby expressing pre-coded instructions which code for new functions, tissues and species. By contrast, the deletion of an active gene may result in evolutionary leaps, or conversely, extinction. Deletions and duplications, coupled with the transposition of the gene or its copy to a different region of the genome, can also obscure the prokarotic or viral origins of the original gene.

Gene loss, like gene conservation, is a major force is evolution. For example, a comparison of the numbers of ancestral gene clusters with those of extant animals such as the nematode, fly, mouse and human, has established that extant bilaterian animals have retained more than 3500 gene clusters of the ancestral gene set, and have lost more than 1600 gene clusters (Ogura et al., 2004).

Deleted genes, however, are not necessarily extinguished. If they are not transferred to new locations within the eukaryotic genome they may instead exit the genome, like a plasmid. Once ejected, these deleted genes may be stored in the genome of yet another species or virus. In fact, when copies of genes are transferred from prokaryotes to eukaryotes, the original may also be deleted from the prokaryotic genome and transferred to the viral genome (Lindell et al., 2004; Sullivan et al., 2005, 2006), thus resulting in gene loss (prokaryote) and gene gain (virus, eukaryote). Thus genes donated and transferred to the eukaryotic genome have been simultaneously deleted from the prokaryotic gene pool and this insures that eukaryotes and not prokaryotes evolve. The one-way transfer of genes from prokaryote to eukaryote (and/or virus) has served a specific, highly regulated purpose. It ensures that these genes, when expressed in response to specific environmental or regulatory signals, effect only eukaryotes. Thus, eukaryotes evolve and become more intelligent and complex, not prokaryotes.

In prokaryotes, gene loss is one of the two major evolutionary processes, along with horizontal gene transfer, that contribute to the intensive �gene flux� that seems to have shaped the genomes of these organisms. That is, not only have prokaryotes lost these genes, but coupled with viral genes which regulate gene and whole genome duplication, this has ensured that only the genomes of eukaryotes and not prokaryotes have undergone repeated duplication. There is little evidence of WGD in prokaryotes.

13. EVOLUTION AND GENOME DUPLICATION

There have been repeated episodes of whole gene duplications during the early evolution of eukaryotes and which date back to the emergence of the first eukaryotic cells or their ancestors (Makarova et al., 2005) and thus to the time period when genes were first transferred to Earthly eukaryotes by prokaryotes and viruses. Reconstruction of ancestral gene repertoires has identified 4137 orthologous gene sets leading back to the last multicellular eukaryotic common ancestor, and 2150 orthologous sets in the hypothetical first unicellular eukaryotic common ancestor, which is indicative of WGD coupled with deletions following gene donation (Makarova et al., 2005).

There is evidence to suggest that the genome may be duplicated at least every 100 million years (Lynch et al., 2001; Lynch and Conery 2000), though in fact the frequency is as yet unknown. Therefore majority of the genes in most genomes of cellular life have undergone at least one duplication at some point during evolution (Lynch 2007; Koonin et al., 1996) and probably many times that.

Whole genome duplications have occurred in almost all lineages, including yeast (Wong et al., 2002; Vision et al., 2000; Kellis et al., 2004; Dietrich et al., 2004), fish (Van de Peer et al., 2003; Jaillon et al., 2004; Taylor et al., 2001), frogs (Tymowska et al., 1977; Jeffreys et al., 1980) and plants (Blanc and Wolfe 2004). The relatively large and complex vertebrate genome appears to have been duplicated at least twice (McLysaght et al., 2002; Dehal and Boore 2005). Gene deletions and expulsions, however, obscure the actual frequency so it is yet unknown how often and how many times the genome has been duplicated.

Whole genome duplications coupled with massive deletions are related to the divergence of species and evolutionary transitions. For example, the number of ancestral gene sets at the time of the split of plant�animal�fungi and the divergence of bilaterian animals, is estimated to be 2469 and 6577, respectively (Ogura et al., 2004). There is a 2.7-fold increase in the number of gene clusters during the period from the evolutionary split of plant�animal�fungi and the divergence of bilaterian animals (Ogura et al., 2004). Therefore, it is evident that single genes are repeatedly duplicated and cluster together.

Single gene and whole genome duplication played a central role in the primary radiation of chordates (Dehal and Boore 2005) during the Cambrian explosion 540 million years ago. There followed additional duplications during chordate evolution, thereby forming many of the gene families of vertebrates (McLysaght et al., 2002).

Dehal and Boore (2005) reconstructed the evolutionary relationships of all gene families from the complete gene sets of tunicate, fish, mouse, and human, and determined when each gene underwent duplication relative to the evolutionary tree of each species. An analysis of the global physical organization and genomic map positions of paralogous genes indicates these specific gene families were duplicated prior to the fish�tetrapod split, some 400 million years ago. This was followed by two distinct genome duplication events early in vertebrate evolution as indicated by clear patterns of four-way paralogous regions covering a large part of the human genome (Dehal and Boore 2005).

Large-scale genomic events marked the transition and divergence between yeast and fungi (Liti and Louis, 2005) chordates and non-chordates (McLysaght et al., 2002), fish and tetrapods (Dehal and Boore 2005), and then once or twice more after vertebrates began to colonize the surface of Earth (Dehal and Boore 2005).

In fact, the genome may have been duplicated dozens of times over the course of evolutionary history (Lynch and Conery 2000; Lynch et al., 2001) thereby triggering the transition and divergence between numerous species, ranging from yeast and fungi (Liti and Louis, 2005) to chordates and non-chordates (Dehal and Boore 2005; McLysaght et al., 2002) and primates and humans.

Gene and whole genome duplication are crucial mechanisms of evolutionary innovation and when coupled with regulatory genes contributed by prokaryotes and viruses, enabled the genomes of eukaryotes to become increasingly complex as well as larger in size. This allowed for multiple copies of the same genes to appear in divergent species and to be passed down until a regulatory or environmental signal triggered their activation. Multiple gene activation also insures that multiple copies of complex cellular structures can be created, such as those contributing to the eyes and brain.

Gene duplication appears to provide the impetus for major evolutionary transitions and triggered the emergence of new species in the absence of obvious intermediaries or transitional species. The duplication of all genes at the same time induced rapid and extensive evolutionary change; i.e. the emergence of new species from old. Whole genome duplication also enabled the entire expanded gene repertoire to evolve together and reach a greater level of interaction and complexity as compared to single gene duplications.

Duplication is often followed by accelerated sequence evolution as well as rearrangement of a gene, an evolutionary mode that obliterates detectable connections to the original gene source. Moreover, although numerous genes might be retained, other duplicated genes or the original might be quickly eradicated (Wolfe 2001) thus erasing the genetic footprints that would lead back to the prokaryotic or viral source. This would make it appear that a new gene has emerged, when it is instead a duplicate, because its origins are no longer apparent. In fact, the vast majority of duplicated genes are subsequently deleted (Dehal and Boore 2005) or ejected from the genome; an event which may also lead to freeing the original, or the duplicate, from inhibitory restraint, and which can erase all evidence of genome duplication (Dehal and Boore 2005).

14. GENE LOSS & GENE EXPRESSION

Gene loss and gene gain appear to be hallmarks of evolutionary transitions and metamorphosis; just as genes are turned on and off during embryogenesis and development. Therefore, in addition to genes being turned off thus resulting in the absorption of tissues or cellular apoptosis, genes are also pruned from the genome just as species are pruned from the tress of life whose characteristics were shaped by those genes (Joseph 2009d).

Lineage-specific gene loss is one of the major evolutionary processes that have been brought to light by comparative analyses of gene sets from completely sequenced genomes (Aravind et al. 2000; Moran 2002). Genome analysis has revealed the extensive loss of genes after WGD, in yeast (Katinka et al. 2001; Scannell et al., 2007; Wolfe and Shields 1997), plants (Soltis et al., 2008; Tuskan et al., 2006), and chordates (Dehal and Boore 2005; Durand 2003; McLysaght et al., 2002).

Gene loss without replacement is a common phenomenon in many genomes and appears to play an important role in shaping genome content (Snel et al. 2002) and evolutionary transitions. The extent of gene loss can be dramatic, and it can occur relatively rapidly under a strong selective pressure (Baumann et al. 1995). In this regard, massive gene loss may be directly linked to mass extinction events (Joseph 2009d).

Although genomes of parasites expose the most striking cases of massive gene loss, a possible function of deletion following transfer, the fact is: substantial gene loss has occurred in all phylogenetic lineages (Snel et al. 2002; Mirkin et al. 2003).

The eradication of the original gene may also play a role in the expression of the duplicate. Once duplicated these genes or their duplicates appear are sometimes freed from inhibitory restraint and are able to undergo an accelerated rate of sequence change thereby inducing the rapid evolution of new characteristics and abilities (Seoighe et al., 2003). Thus after duplication followed by deletion, the duplicate or original genes, now freed of the constraints imposed on the original, can express a precoded function (�neofunctionalization�) which had been repressed (Conant and Wolf 2008).

The "new" function of one gene copy is often a secondary property, or subfunction, that was always present, but which may have been suppressed, or which only came to be expressed when other more dominant functional capabilities were inhibited, suppressed or deleted. Therefore, old functions might be fractionated giving rise to new subfunctions (�subfunctionalization�). That is, the new function was not really "new" but had always been a property of a specific gene that could only be expressed following duplication, or duplication coupled with deletion.

Thus, it is not uncommon for the new paralogs to retain or express distinct subsets of the original functions of the ancestral gene whereas the rest of the functions differentially deteriorate (Lynch and Force 2000; Lynch and Katju 2004)

Duplication and the lessening of regulatory restraints might also make the gene more susceptible and sensitive to environmental triggers. Thus, when the biosphere has been sufficiently biologically altered, single genes or the entire genome may be duplicated, and suppressed functions encoded into silent genes, are then expressed.

15. INTRONS AND GENE EXPRESSION

DNA includes stretches of nucleotides, called exons, that are encoded and expressed to produce various proteins (De Souza et al., 1996). These strings of nucleotides are punctuated, bracketed, framed, and interspersed with long stretches of non-encoding DNA, called introns (Belfort, 1991, 1993; Breathnach et al., 1978; Buchman and Berg 1988; Witkowski, 1988). In complex multicellular organisms introns are often 10-fold longer than exons (De Souza et al., 1996). They also signal which lengths of exons are to be expressed (Belfort, 1991, 1993; Breathnach et al., 1978; Witkowski, 1988). Introns are typically snipped out as strings of exons are transcribed via RNA intermediaries, into proteins (Breibart et al., 1985; Leff et al., 1986).

What this means is that gene sequences which may have originally been inserted into the eukaryotic genome by prokaryotes and viruses, are regulated by introns which have been inserted by viruses and prokaryotes.

Introns are of particular importance in regulating gene expression (Brinster et al., 1988; Buchman and Berg, 1988; Collis et al., 1990; Lai, et al., 1998; Noe et al., 2003). If different "starter" or "stop" introns are activated this results in different segments or sequence lengths becoming expressed, thereby producing a different product (Belfort, 1991, 1993; Breathnach et al., 1978; Breibart et al., 1985; Leff et al., 1986). Hence, variation and diversity can be differentially induced if different "starter" exons or promoter introns are activated.

Introns have been preserved often in the same places in the genome, over the course of evolution, be it the genes of Drosophila melanogaster (the fruit fly), Caenorhabditis elegans (nematode), mice, or humans ((De Souza et al., 1996; Federov et al., 2002). This extreme conservation and preservation of their positions within genes, attests to their importance in regulating and coordinating evolution and metamorphosis among numerous species. Many are catalytically active and facilitate chemical reactions, even catalyzing their own synthesis (De Souza et al., 1996).

Via the joining of exons after splicing, introns also trigger the synthesis of novel proteins with new properties (Brietbart et al., 1985; De Souza et al., 1996; Leff et al., 1986); that is "novel" and "new" on Earth. They may also promote the creation of multiple copies of the proteins coded by single genes (Brietbart et al., 1985; Leff et al., 1986). In fact, the presence of an intron can increase transcriptional efficiency 100-fold whereas in the absence of the intron these genes may not be expressed at all (Brinster et al., 1988; Lai et al., 1998).

Hence, introns are involved in transcription, translation, signaling, protein synthesis, and regulating which gene sequences or portions of the gene should be expressed or inhibited (Brinster et al., 1988; Brietbart et al., 1985; Buchman and Berg 1988; Collis et al., 1990; Leff et al., 1986; Lai, et al., 1998; Noe et al., 2003). They also create fashion new genes from old genes.

Introns guide or participate in the genetic recombinations between exons, a process called �exon shuffling" (Gilbert, 1978, 1987; Doolittle,1978; Blake, 1978). Exon shuffling is the process where full-length genes are created from exon �pieces� by recombination within the introns (De Souza et al., 1996, 1998, 2003; Fedorov 2001, 2003; Long et al., 1995; Roy 2003; Roy et al., 1999, 2001, 2003). Exon shuffling is associated with the formation of new genes from old genes.

Introns also are implicated in the production of additional genes and even gene clusters which are located deep within the intron (Henikoff et al. 1986; De Souza et al., 1996; Strachan & Read, 1996). Thus, introns may be responsible for producing duplicate genes as well as new genes and clusters of genes, including numerous copies of highly repetitive sequences of nucleotide base pairs (Finnegan, 1989; Henikoff et al. 1986; Peters & Fink, 1982). Indeed, introns, and intronic gene clusters are considered a "hot spot" for homologous recombination (Wahls et al. 1990).

Introns also play a major role in the origin and diversity of proteins by facilitating recombination of sequence coding for small protein/peptide modules (Brietbart et al., 1985; Leff et al., 1986; Koonin 2006). If the length of the code is altered and reframed, or if introns change their positions within the genes, the products produced by the altered code may also undergo subtle or profound changes (Brietbart et al., 1985; Leff et al., 1986). Therefore a variety of tissues and organs can be fashioned thus facilitating evolutionary growth and development, simply through the movement of an intron.

Introns also contain copies of gene sections that have been silenced and suppressed (De Souza et al., 1996). They maintain the "old code" for genes that were once translated into a protein, as well as the codes for genes that have not yet been expressed. Introns are thus implicated in the release of genetically pre-coded traits (de Jong & Scharloo, 1976; Dykhuizen & Hart, 1980; Gibson & Hogness, 1996; Polaczyk et al., 1998; Rutherford & Lindquist, 1998; Wade et al., 1997).

Hence, introns create genes from old genes, recombine pieces of genes, and thus can combine, fractionate, or reconfigure the structure of a gene, thereby creating new functions from the parsing or assimilation of old functions coded by single or multiple genes. Moreover, they can silence or activate the expression of the genes they create or those they regulate.

Introns, therefore, play a major role in evolution acting to regulate gene expression, maintaining copies of genes, and promoting the assembly of new genes and new gene sequences from old genes, and generating multiple copies of the same or a new protein product.

Thus, following the initial donation of introns to eukaryotes, new genes were assembled from old genes (De Souza et al., 1996, 1998, 2003; Fedorov 2001, 2003; Long et al., 1995; Roy 2003; Roy et al., 1999, 2001, 2003), albeit in a highly regulated, coordinated, purposeful fashion, so as to produce specific protein products, thereby promoting evolutionary metamorphosis. The genome began to increase in size and complexity and genes expressed new, albeit precoded functions; which gave rise to new tissues, organs, and the evolution of new species (Duret 2001; Comeron and Krietman 2000) which had been precoded into the genome, even though these new species had never before been see on Earth.

Therefore, introns, which may have originally been donated by prokaryotes (Cavalier-Smith 1991; Martin and Koonin 2006; Sharp 1991; Stoltzfus 1999), as well as viruses, may play a significant role in regulating, copying, and duplicating genes which had also been transferred to the eukaryotic genome by prokaryotes and viruses. Moreover, they appear able to regulate the manufacture of new proteins and thus guide the evolution of new tissues, organs, and species. These are not random events, but are under precise regulatory control.

16. PROKARYOTIC AND VIRAL ORIGINS OF INTRONS AND RIBOZYMES

Numerous introns invaded eukaryotic genes at the outset of eukaryogenesis as the first Earthly multi-cellular eurkayotes were being fashioned (Martin and Koonin 2006; Rogozin et al., 2005), and thus at the earliest stages of eukaryote evolution (Rogozin et al., 2005). All eukaryotes whose genomes have been sequenced, including parasitic protists, have been shown to possess introns (Doolittle 1978; Gilbert 1978; Mattick 1994; Deutsch and Long 1999; Nixon et al. 2002; Simpson et al. 2002; Vanacova et al. 2005). Even the simplest of eukaryotes contain introns as well as spliceosomal proteins within their genomes (Collins and Penny 2005). Introns then continued to be donated or duplicated as eukaryotes evolved.

In addition to viruses, both archae and bacteria appear to have supplied eurkaryotes with numerous introns (Martin and Koonin 2006), perhaps flooding the eukaryotic genome with introns and transposable elements at the earliest stages of eukaryosis (Cavalier-Smith 1991; Martin and Koonin 2006; Sharp 1991; Stoltzfus 1999), and then periodically thereafter on an as-needed-basis. A massive initial influx of introns would also explain why ancient eukaryotes (Roy 2006) including the last common ancestors for eukaryotes, possessed high intron densities (Carmel et al., 2007; Csuros et al., 2008; Roy 2006).

Moreover, archae may have contributed introns, including ribosomal introns and protein sequences to the eukaryotic genome (Watanabe et al., 2002). Some archae genomes contain genes that are dotted with micro-introns and some archae proteins are also bracketed by introns (Watanabe et al., 2002) as is common in eukaryotes.

24. INTRONS & RNA

Some introns may also propagate at the RNA level including within messenger RNA. Messenger RNA (mRNA) is transcribed from a DNA template and contains the codes for creating specific protein products which it transports to ribosomes for protein synthesis. These introns indicate which portions of the code are to be translated and transcribed and are then snipped out and are reinserted (spliced) into another region of the genome which is without an intron.

Presumably, the new intron-containing RNA is reverse-transcribed and undergoes gene conversion leading to a new intron. Therefore, via reverse-splicing an excised intron sometimes reintegrates back into a different site in the same mRNA (Coghlan & Wolfe 2004; Tarr�o et al., 1998) thereby exerting multiple coordinated influences on gene expression and protein synthesis.

Introns may have been the original information source for the creation of genes which code for mRNA. Likewise, genes involved in mRNA processing and splicing, and germline-expressed genes, preferentially gain introns (Roy 2004). By contrast, introns/TEs are generally excluded from mRNAs of highly conserved genes (van de Lagemaat et al., 2003).

A gene ontology analysis has demonstrated that novel introns are unusually frequent in genes with mRNA processing functions, relative to germ-line-expressed genes. This suggests that it is the function of these genes, rather than their mode of transcription, that makes them amenable to gaining introns (Coghlan & Wolfe 2004). Thus, introns regulate functional expression, and they may have been inserted by Viruses with an RNA genome.

Thus introns regulate gene expression or suppression and control the transposition of these introns to different regions of the genome. These properties enabled introns to coordinate the expression or suppression of a wide network of genes.

For example, RNA not only serves as a messenger but can interfere with and inhibit and silence gene expression (Hall et al., 2002). This is accomplished, in association with transposons/introns via heterochromatin formation whose repressive capacity is mediated by components of RNA interference machinery (RNAi). This RNAi machinery acts to nucleate heterochromatin assembly and can initiate and propagates regional heterochromatic inhibition and gene silencing (Hall et al., 2002; Volpe 2002). RNAi in association with introns/transposons can even control chromosome segregation and the expression of large chromosome domains (Grewal and Moazed 2003).

Thus, introns and transposons can exert regulatory control of individual genes, chromosomes, and thus the entire genome.

TE-induced genetic alterations and changes in regulatory sequences, are of extreme evolutionary significance to their hosts and to the metamorphosis and evolution of future species (Britten 1996). TEs, especially when inserted into introns, can alter the size and arrangement of whole genomes, induce changes in single nucleotides, and generate new genetic variation on a scale, and with a degree of sophistication, ranging from subtle to dramatic alterations in the development and organization of tissues and organs (de Jong & Scharloo, 1976; Dykhuizen & Hart, 1980; Finnegan, 1989; Dibb & Newman, 1989; Gibson & Hogness, 1996; John & Miklos, 1988; Kuhsel, et al. 1990; Moran et al., 1999 Polaczyk et al., 1998; Rutherford & Lindquist, 1998; Strachan & Read, 1996; Wade et al., 1997). Such changes appear most likely if these insertions occur in coding regions and often confer useful traits on the host, as well as guide, coordinate, and regulate evolution and metamorphosis.

17. GROUP II SELF-SPLICING INTRONS

Introns exert a significant regulatory influence over gene expression and may have played a role in the seperation between transcription and translation (Roy and Gilbert 2006). Introns are also linked to viruses, including viral RNA which promotes transcription, translation, and replication functions. It is also possible that viruses and/or bacteria may have provided two types of RNA genes to the eukaryotic genome--mRNA and iRNA. These highly structured Eukaryotic RNAs are also linked with group II introns and might have originated from introns in the bacterial progenitor of the mitochondria (Blumenthal, 2005; Toro et al., 2007) and which are directly linked to retroviruses.

Again, as emphasized, viruses serve as genetic storehouses, and prokaryotes can also use viruses to insert genes into eukaryotes. Therefore, since group II introns (including some ribozymes), are linked to highly mobile retroelements (Belfort et al., 2002; Lambowitz et al., 1999; Lambowitz and Zimmerly 2004) they were likely inserted into the eukaryotic genome by viruses.

Ribozymes are an RNA enzyme which have catalytic properties and are implicated in the synthesis of RNA polymerase which acts to copy sequences of introns. Many ribozymes appear to be derived from viruses, and act to catalyze the splicing of their flanking exons (Bonen and Vogel 2001; Michel and Ferat 1995). As ribozymes are found in all three domains of life (Dai and Zimmerly 2003; Dai et al., 2003) this again indicates that highly regulated purposeful coordinated mechanisms guide these processes and interactions.

Group II introns (retrotransposons) which may have originated in or were donated exclusively by retroviruses. They are also found in all three domains of life (Dai and Zimmerly 2003; Dai et al., 2003). Group II introns are highly mobile and can move about the genome in a purposeful, highly coordinated and regulated fashion. (Belfort et al., 2002; Lambowitz et al., 1999; Lambowitz and Zimmerly 2004).

Group II introns may also be progenitors of nuclear spliceosomal introns (Cavalier-Smith 1991; Jacquier 1990; Sharp 1991). Group II self-splicing introns are also present in the genomes of many bacteria (Cavalier-Smith 1991; Koonin 2006; Roy 2006; Stoltzfus 1999). Thus, spliceosomal introns may have evolved from group II self-splicing introns which originated in the genome of viruses or the bacterial progenitor of mitochondria.

Group II self-splicing introns also evolved in partnership with the spliceosome, both of which may have originated in organelles which transfered type II introns into the nucleus (Cavalier-Smith, 1985; Rogers, 1989). Organelles are linked to a bacterial symbiont which took up residence in eukaryotes billions of years ago.

Self-splicing (spliceosomal) introns snip out introns and interrupt sequences of protein-coding genes and are among the defining features of eukaryotes (Doolittle 1978; Gilbert 1978; Mattick 1994; Deutsch and Long 1999). Numerous spliceosomal introns invaded the genes of the multi-cellular eukaryote during eukaryogenesis. Self-splicing introns can be traced back to the earliest stages of eukaryotic evolution, and are directly linked to viral and bacteria group II introns, (Toro et al., 2007), bacterial operons (Garrett et al., 1994), archae (Lake et al. 1984; Lake 1988; 1998; Rivera and Lake 1992; Rivera and Lake 2004; Vishwanath et al. 2004) mitochondria (Blumenthal, 2005; Dyall et al., 2004; O'Brien 2002). They serve the basic machinery of gene expression: transcription, splicing, and translation (Blumenthal, 2005).

Likewise, spliceosomal proteins are part of the core cellular machinery that is conserved across eukaryotes, and are sometimes located within operons (Blumenthal and Gleason, 2003; Blumenthal et al., 2002; Garrett et al., 1994; Hill et al., 2000). Operons are sequences of nucleotides which include several structural genes and a promoter, and which produce messenger RNA (mRNA), via transcription by an RNA polymerase (Salgado et al., 2000). Operons are believed to have originated in the prokaryote genome (Che et al., 2006; Ermolaeva et al., 2001) and regulate the expression of various genes, depending on environmental conditions (Salgado, et al., 2000). The regulation of gene expression is accomplished by the binding of a repressor to the operator to prevent transcription, or by inserting an inducer molecule which binds to the repressor thereby allowing expression (Blumenthal et al., 2002; Salgado, et al., 2000). Introns have retained the operon capacity to repress or selectively express genes sequences.

Self-splicing Group II introns serve as catalytic RNAs (ribozymes) and mobile retroelements, which reinsert themselves into the genome after they are snipped out (Finnegan, 1989; Moran et al., 1999; Roy and Gilbert 2006). In this way, adjoining exon sequences can be translated via RNA, after which the Group II introns reinserts itself. They can also change their position within the genome and can influence the expression of different sequences of genes in a step-wise temporal-sequential fashion (Dibb & Newman, 1989; John & Miklos, 1988; Kuhsel, et al. 1990).

Group II introns therefore, have the mobile characteristics of transposons and retrotransposons and also serve as transposable genetic elements (Crick, 1979; Coghlan and Wolfe, 2004; Finnegan, 1989; Hickey 1992; Moran et al., 1999). They have viral characteristics. Likewise, some novel introns appear to arise by transposon insertions (Crick, 1979; Dibb & Newman, 1989; John & Miklos, 1988; Kuhsel, et al. 1990). Conversely, some retrotransposons, which have the ability to reinsert themselves, appear to have evolved from mobile group II introns which were inserted into the eukaryotic genome by viruses.

Group II introns are also progenitors of nuclear spliceosomal introns (Cavalier-Smith 1991; Jacquier 1990; Sharp 1991), and can splice together exons (Bonen and Vogel 2001; Michel and Ferat 1995) thereby creating new gene products, and contributing to speciation (Volff et al. 2000, 2001c) and evolutionary metamorphosis. Further, they can leap to different locations in the genome, transcribing genes which had been silent, or suppressing genes which had been active, thereby coordinating gene expression involving a variety of tissues and organs (Seifarth et al., 2005).

In the human genome, these retroviral sequences encode tens-of-thousands of active promoters and can initiate transcription of adjacent human genes and regulate human transcription on a large scale (Conley et al., 2008; Jordan et al., 2003; van de Lagemaat et al., 2003). Thus, these viral elements have exerted a major influences on the evolution of the human-non-human genome. There is nothing random about these viral-genomic interactions, as they are under precise genetic regulatory control and are regulated in a complex, precise manner comparable to cellular genes (de Parseval et al., 1999; Knossl et al., 1999; La Mantia et al., 1992; Lee et al., 2003; Nelson et al. 1996; Sjottem et al., 1996).

GROUP III INTRONS

Group II and III intronic retroelements often insert themselves into exons. Once inserted they are quickly integrated within these exonic sequence (Hallick et al., 1993) and can easily suppress these genes. Group III intron are sometimes formed from the domains of two individual group II introns (Hong and Hallick, 1994). The group III introns and group II introns also share a common evolutionary ancestor, which is linked to the alpha bacteria progenitator as well as archae.

These introns possess the genetic mechanisms which allow them to be efficiently spliced out of transcripts, and to reinsert themselves in another part of the genome. They are able to demarcate coding sequences and to regulate gene expression in different regions of the genome, perhaps simultaneously as well as sequentially. Thus they can guide the activity of a number of gene networks to coordinate gene expression.

Therfore, introns, which may have originated in prokaryotes, can duplicate and give birth to themselves, and possess the genetic machinery which enables them to propagate throughout the genome and to regulate gene expression via silencing and restriction. As is also demonstrated by their highly conserved nature, these are not chance, or random events.

Introns and Transposable Elements Group II introns, which are derived from retroviruses, can act as retrotransposons, and are highly mobile retroelements (Belfort et al., 2002; Beauregard, et al., 2008; Lambowitz et al., 1999; Lambowitz and Zimmerly 2004) which regulate gene expression. Introns and transposable elements (TEs) are in fact intimately linked and in some instances are indistinguishable. Eukaryotic genomes contain numerous TEs, many of which are found in introns (Nekrutenko and Li 2001). Most eukaryotic genomes are littered with introns and transposable elements, and many TEs are located within introns or have been inserted into exons over the course of evolution (Nekrutenko and Li 2001). Hallick et al., 1993). Therefore, introns can be regulated by introns which are inserted during different periods of evolutionary development and in different species.

Coghlan and Wolfe (2004) have examined intron matches and found that around 70% have a nucleotide identity identical to transposable elements. In many cases the new intron is homologous to a transposon and to another intron, indicating the intron acted as a transposon and made a copy of itself which was inserted into another region of the genome. In this manner introns duplicate themselves, jump to different regions of the genome, and can regulate other introns and coordinate gene expression in a wide range of gene networks. In some cases what appears to be a new intron is in fact an intron reinsertion, transcript retroposition, intron duplication, or gene conversion. If due to duplication then deletion of the original intron following transposition, then intron gains and losses may be one and the same. However, intron loss may also be a function of transfer to another organism, or the intron may not have been lost at all, but is in hiding; that is, it inserts itself inside another intron.

23. TRANSPOSONS, INTRONS & GENE ACTIVATION VS GENE EXPRESSION

Introns insert themselves into introns. The genomes of numerous species contain introns-within-introns (twintrons), indicating that introns are also targets of intron insertions (Copertino and Hallick 1991; Doetsch et al., 2001). Thus introns which act as transposable elements (TEs) may regulate exons and other introns.

TEs inserted into introns also affect RNA processing, and intronic TEs can render its host gene susceptible to siRNA-mediated transcriptional gene silencing (Doetsch et al., 2001). Therefore, they can turn genes on or off.

The majority of all introns in the eukaryotic and human genome have Alu insertions (Grover et al. 2004) which were derived from retroviruses. These Alu enzymes cut up foreign DNA in a process called "restriction" and are also found in bacteria and archaea (Arber and Linn 1969; Kr�ger and Bickle 1983). Possibly they were donated to the eukaryotic genome by viruses, perhaps as a protection against other viruses to restrict or regulate the insertion of additional genes or regulatory elements. "Restriction", therefore, is yet another means by which introns can silence genes, including nearby genes, and through which it can regulate which genes are inserted into the genome.

Transposons/introns, in association with RNA, also serve as regulators of gene expression and chromosome segregation by inserting and introducing heterochromatin which prevents gene expression by wrapping the gene in a protective protein coat (Hall et al., 2002; Grewal and Moazed 2003; Grewal and Martienssen, 2002; McClintock 1950; Volpe et al., 2002). Heterochromatin is characterized by a high density of transposons (Volpe et al., 2002). Gene silencing is also accomplished via RNA and the methylation of histones (Grewal and Martienssen, 2002; Hall et al., 2002). TE insertion therefore, can disrupt the coding sequences of a gene and inhibit the production of viable gene products.

26. GENE ACTIVATION & SUPPRESSION

Genes expression can be restricted and inhibited by a variety of mechanisms and proteins, such by "restriction" via Alu enzymes (Arber and Linn 1969; Kr�ger and Bickle 1983) which are linked to retroviruses, or the binding of a repressor molecule or protein to the operator to prevent transcription (Blumenthal et al., 2002; Salgado, et al., 2000). Inhibition can also be accomplished via methylation and/or the generation of heterochromatin (Waterland, 2006, Waterland and Jirtle, 2003; Yoder et al., 1997).

Further, TEs inserted into introns can inhibit mRNA processing, and can render numerous genes susceptible to siRNA-mediated transcriptional gene silencing (Doetsch et al., 2001). Heterochromatin formation and its repressive capacity are also mediated by RNA interference (RNAi) machinery (Grewal and Moazed 2003; Hall et al., 2002; Volpe et al., 2002). Therefore, they can turn genes on, or off.

Transposons which use the gene replication machinery to reproduce themselves, also utilize methylation to prevent their own replication and to prevent the expression of nearby genes (Yoder et al., 1997; Rakyan et al., 2002). Most transposable elements in the mammalian genome, along with the genes positioned near them, are silenced by methylation (Yoder et al., 1997; Rakyan et al., 2002). DNA methylation involves four atoms, the methyl group, which attaches to and coats the gene thus silencing the gene by preventing its expression. Methylation is commonly employed to inactivate a variety of genes (Wolff et al., 1998; Yoder et al., 1997; Van den Veyver 2002). However, by inactivating a TE, methylation may instead induce gene expression.

Transposable elements, therefore, in conjunction with methylation, "restriction" siRNA-mediated transcriptional gene silencing, and the generation of heterochromatin commonly silence or activate various genes, and can cause considerable phenotypic variability, making each individual mammal a "compound epigenetic mosaic" (Whitelaw and Martin, 2001).

These mechanisms mediating gene silencing and activation have also been adopted to evolve new traits (Liu et al., 2004). TE insertion within promoters, introns, and untranslated regions, can directly trigger incredible genetic variation and the full gambit of phenotypes, ranging from subtle epigenetic regulatory perturbations to the complete loss of gene function (Kidwell and Lisch, 1997; Wessler, 1988). That is, by turning genes on and off, different regions of a gene network may be activated or silenced, and different products can be produced or eliminated.

18. INTRONS ARE CONSERVED

The positions of introns and numerous spliceosomal and spliceosome-associated proteins, have been highly conserved in the same locations and positions within the genes of numerous species (Anantharaman et al., 2002; Collins and Penny 2005; Federov et al., 2002). Thousands of introns are located in the exact same regions of the genome, even when comparing the genes of fungi and humans (Federov et al., 2002). This conservation of position and location indicates they exert extremely important influences on the coordination of gene regulation and expression even among different species, possibly even acting to coordinate the evolution of various species in relation to one another.

Studies have shown that highly conserved, shared intron positions are common in animal, plant and fungal genes (Federov et al., 2002). In one study it was found that 14% of animal introns match plant positions, and that ≈17�18% of fungal introns match animal or plant positions (Fedorov et al., 2002), even though animals and plants diverged from any common ancestors over a billion years ago (Wang et al., 1999). Indeed, the three-way split between plants, animals and fungi has been estimated to have occurred around 1.6 bya, whereas the the basal animal phyla (Porifera, Cnidaria, Ctenophora) diverged between 1.2 to 1.5 bya (Wang et al., 1999). Conserved introns have an ancient pedigree.

Federov et al., (2002) examined 30 nonrelated genes with the highest numbers of common animal�plant introns and found that "60% of the fungal introns have positions common to animal and/or plant introns, and 39% of fungal introns are common simultaneously to both plant and animal introns. This exceptionally high abundance of introns with positions common to all three taxa of animals, plants, and fungi strongly supports the antiquity of these common intron positions."

In yet another genomic study (Rogozin et al., 2003), intron positions were compared in 684 orthologous gene sets from 8 complete genomes of animals, plants, fungi, and protists/parasite. Approximately one-third of the introns in the protist parasite were shared with at least one crown group of eukaryote; indicating that these introns have been conserved for over 1.2 billion years of evolution.

Between 10% to 20% of intron positions and other genomic features without obvious functions have been conserved throughout the evolution of eukaryotes leading up to an including in humans (Bejerano et al., 2004; Fedorov et al., 2002). However, the fact that these functions are not obvious is not an indication of a lack of importance. These unknown functions may not be expressed except in future species. "What is conserved is functionally relevant" should be considered a central tenant of biology, even if the functions are not yet obvious.

Although conserved, sequences within introns have changed considerably over the course of evolution, sometimes by orders of magnitude, and at a faster pace than those of exons (Federov et al., 2002). Thus, these highly conserved introns are obviously internally active whereas the genes they control and regulate undergo relatively fewer changes, other than being turned on and off by introns. It is this activation vs silencing of genes which impacts the rate and trajectory of evolution, and possibly the extinction of species, which, like introns, can drop out of the gene pool.

19. INTRON GAINS & LOSSES

Introns have been donated to the eukaryotic genome by archae, bacteria, and viruses. They have acted in a precise, highly choreographed, genetically regulated fashion to activate, silence, and duplicate genes which had also been transferred to the eukaryotic genome by viruses, archae, and bacteria. Further, once their genetic mission has been accomplished, these introns may be deleted, or duplicated and transferred to yet another region of the genome. Introns, therefore, have play a major role in the evolution of all species, leading up to and including humans.

The donation or duplication and deletion of introns may have occurred throughout eukaryotic evolution, with introns coming and going (Roy and Gilbert 2006). Eukaryotes harbor multiple introns per gene (Logsdon 1998; Mourier and Jeffares 2003; Jeffares et al. 2006), requiring hundreds of thousands, if not millions of individual introns to have been donated or duplicated throughout eukaryotic evolution and even during recent evolutionary history (Cavalier-Smith, 1985; Logsdon 1998; Palmer and Logsdon, 1991). These finding imply an active role of viruses in the continual transfer of introns into the eukaryotic genome. However, gains are often accompanied or followed by losses, which again may imply transfer back to the viral genome where they may be transformed and copied into RNA.

It is inferred that a relatively high intron density was reached early in the metamorphosis of eukaryotes (Carmel et al., 2007; Cavalier-Smith 1991; Csuros et al., 2008; Martin and Koonin 2006; Roy 2006; Sharp 1991; Stoltzfus 1999). It has been estimated that the last common ancestor of eukaryotes contained >2.15 introns/kilobase. The last common ancestor of multicellular life acquired even more, harboring ∼3.4 introns/kilobase, a greater intron density than in modern insects, most extant fungi and some animals (Carmel et al., 2007). These findings indicate that a massive intron duplicative event or flood of insertions coupled with deletions occurred at the earliest stages of multi-cellular evolution. Among the top six intron-rich species, five are ancestral forms, indicating that some subsequent species have lost introns, whereas initially the number of introns actually increased during the evolutionary leap from uni-cellular ancestor to the first multi-cellular ancestor and to the first diverging species.

Just as prokaryotes may have lost introns upon donating them in massive numbers to ancestral eukarotes, the higher density of introns in ancient vs more recent species, also suggests that introns play a major role in evolution and then drop out in those species which will no longer evolve. Intron loss may prevent species from evolving. Therefore, introns have been eliminated from the genomes of those in a state of prolonged stasis and evolutionary equilibrium. The deletions of introns from prokarotes (and their storage in viruses) also insures that eukaryotes and not prokaryotes evolve.

The evolution of eukaryotic genes is characterized by numerous intron gains and losses (Carmel et al., 2007) and different species vary dramatically in their intron density, ranging from a few introns per genome to over eight per gene (Logsdon 1998; Mourier and Jeffares 2003; Jeffares et al. 2006). Introns are prevalent in complex eukaryotes but rare in the simple ones (Cavalier-Smith, 1985; Logsdon 1998; Palmer and Logsdon, 1991), indicating that the acquisition or duplication of introns is associated with species which have evolved, and which may continue to evolve.

For example, there has been elevated rate of intron loss in several lineages, such as fungi and insects, nematodes, and arthropods (Carmel et al., 2007; Rogozin et al., 2003); species which no longer appear to be evolving, and which may have diverged from vertebrates around 1.2 bya (Wang et al., 1999). Thus, in non-vertebrates the rate of intron loss and gain have decreased in the last 1.3 billion yr. (Carmel et al., 2007). Further, in these lineages and in the last 100 to 300 million years, there has been a dramatic decrease in intron duplicative events, such that gains decreased faster than the decrease in losses, such that many lineages had only limited intron gains (Carmel et al., 2007; Rogozin et al., 2003).

Nematodes are characterized by a high number of events, with losses being more plentiful than gains (Cho et al. 2004; Coghlan and Wolfe 2004). Fungi also show more losses than gains (Nielsen et al. 2004). Recent intron losses are also seen in plant genes (Charlesworth et al., 1998).

Whereas many ancestral introns have been lost in fungi and other lower forms, they are retained in the genomes of higher vertebrates (Rogozin et al., 2003) many of which evolved in the last 40 million years. Many "higher" vertebrate species have continued to gain introns, albeit at a rather slowed pace, whereas "lower vertebrates" appear to be losing introns and to be experiencing a rapid reduction in gains (Fedorov et al. 2003; Babenko et al. 2004; Coulombe-Huntington and Majewski 2007). A survey of mammalian genes found six cases of intron losses in rodents relative to human (Roy et al., 2003). In fact, for most extant species, the total number of losses outnumbers the number of gains (Carmel et al., 2007).

Therefore, intron gains and losses may be an indication of the evolutionary status of any particular species, if they are in a state of stasis, going extinct, or if their genome is primed to undergo additional evolutionary leaps. Thus intron gain, retention, or loss, may indicate if a species may continue to evolve or go extinct.

Most introns may have been acquired from viruses. Gene gain may also represent new viral invasions and the insertions of viral elements. By contrast, genes which are lost may be transferred back to viruses by those species who evolution has come to an end.

The accelerated rate of loss in many species may also indicate that these introns have been donated to the genomes of yet other species where they are exerting regulatory and evolutionary influences on gene selection and expression. As introns are quite mobile, they can also jump from location to location like a plasmid, coordinating the expression or suppression of a wide range of genes simultaneously and thus making it appear that introns have been lost, or gained, when they have merely moved to a new location; or, perhaps, like a virus, jumped to the genome of a different species where it then begins exerting regulatory influences on gene expression.

25. INTRONS INFECT OTHER SPECIES

Between 35% to 50% of the human genome is ultimately derived from transposable elements (International Human Genome Sequencing Consortium 2001; Lander et al., 2001; Smith 1996; Yoder et al., 1997), and there are many examples of human genes derived from single transposon insertions (Nekrutenko and Li, 2001; Sakai et al. 2007). Moreover, large numbers are found in human protein coding genes (Nekrutenko and Li, 2001).

In a study of genome-wide impact of transposable elements on evolution, Nekrutenko and Li (2001) found that almost 89% of these TEs reside within 'introns' and were recruited into coding regions as novel exons, such that it appears that TE insertion might create new genes (Nekrutenko and Li, 2001) and recruit new exons (Sakai et al. 2007), which would in turn, affect and accelerate species divergence. Numerous studies have in fact found that TEs in the mammalian genome promote the variation and diversification of genes, and affect the expression of many genes through the donation of transcriptional regulatory signals (Thornburg et al., 2006; van de Lagemaat et al., 2003; Jordan et al., 2003).

TEs therefore, contribute to pre-transcriptional gene regulation, especially by moving transcriptional signals within the genome which in turn leads to new gene expression patterns (Thornburg et al., 2006) and the creation of new genes from old genes (Nekrutenko and Li, 2001; Sakai et al. 2007). Further TEs are involved in gene duplication and the creation of large numbers of interspersed repetitive sequences (Smit 1996). By contrast, mRNAs of highly conserved genes are generally devoid of TEs (van de Lagemaat et al., 2003).

TEs are more frequent in duplicate than single copy protein coding genes (Sakai et al. 2007) indicating they are involved in gene duplication and diversity (van de Lagemaat et al., 2003) and not gene conservation. Thus TEs serve as recombination hot spots and may express or create specific cellular functions, through the control of protein translation and gene transcription (Thornburg et al., 2006). In fact because many TEs are taxon-specific, their integration into coding regions could accelerate species divergence and contribute to sudden bursts of evolutionary development (Jordan et al., 2003; Morgan 1993; Nekrutenko and Li, 2001; Sakai et al. 2007; van de Lagemaat et al., 2003).

Moreover, gene classes which react to external environmental stimuli, have transcripts enriched with TEs (van de Lagemaat et al., 2003). In addition, TEs are intimately involved in the simultaneous regulation of multiple genes (Jordan et al., 2003). Thus TEs can trigger gene expression in numerous genes simultaneously in response to changing environmental conditions; and this may include whole genome duplication and/or explosive evolutionary leaps after long periods of evolutionary equilibrium.

The life cycle of TEs in any single phylogenetic lineage can apparently last for many thousands or millions of years and can be considered as a succession of six phases: dynamic replication, movement to another region of the genome, transfer to another species, activation, inactivation, degradation (Kidwell, 1993; Miller et al., 1996).

TE are intrinsically parasitic (Doolittle and Sapienza, 1980; Dujon, 1989; Orgel and Crick, 1980; Hickey 1982; Kiyasu and Kidwell 1984; McDonald 1993; Yoder et al., 1997), and can easily duplicate themselves (Plasterk and Sherratt, 1995) and invade new species (Dujon, 1989; Dujon et al., 1989; McDonald 1993). A proclivity for horizontal transfer is consistent with the role of TEs as genomic parasites. TEs, therefore, also act as plasmids.

Horizontal transfer to another host lineage provides the opportunity for active TEs to begin the cycle over again in yet another species (Dujon, 1989; Dujon et al., 1989; Hurst et al., 1992; Kidwell, 1993; 1994; McDonald 1993) or to insure that all members of the same species undergo the same genetic and evolutionary changes at the same time (McDonald 1993).

Moreover, this enables these intronic TEs to coordinate gene expression among multiple members of the same or divergent species, such that different species may evolve in tandem or develop complimentary traits at the same time.

These TEs can survive over long periods of evolutionary time by spreading throughout numerous genomes belonging to numerous divergent and subsequent species. However, once transferred, transposed, and inserted, these TEs may serve only to inhibit gene expression (Waterland and Jirtle, 2003; Yoder et al., 1997). It may take hundreds of millions or even billions of years, before these genes become active and begin expressing new functions, new characteristics, and even new species; and this may require major changes in the environment and the elimination of suppressive influences.

20. VIRUSES, INTRONS & PUNCTUATED EVOLUTIONARY EQUILIBRIUM

The original introns were likely highly mobile, retrotransposable genetic elements which actively invaded the eukaryotic genome at the outset of eukaryotic evolution, relying in part on internally encoded enzyme activities for mobility. Once introns were transferred to the eukaryotic genome by archae, bacteria, and viruses, they then punctuated and framed numerous protein-coding genes and played crucial roles in recombination, gene creation, coordination of transcription and translation, the emergence of the spliceosome, as well as the nucleus, linear chromosomes, telomerase, the ubiquitin signaling system, inhibition and expression, gene duplication and creation, and the expansion of the genome (Comeron and Kreitman 2000; De Souza et al., 2003; Duret 2001; Fedorov 2003; Koonin 2006; Gilbert 1978, 1987; Long et al., 1995; Mattick 1994; Prachumwat et al., 2004; Roy and Gilbert 2006; Tonegawa et al., 1978).

Thus, introns which were donated by prokaryotes and viruses, acted on genes which had been transferred by viruses and prokaryotes to the eukaryotic genome, thereby creating new genes from old genes, expressing pre-coded traits, and giving rise to a progression of increasingly complex species. Introns play a major role in the regulation of evolutionary metamorphosis by acting on genes which originated in prokarotes.

The donation of introns by prokaryotes following the metamorphosis of the first eukaryotes, also explains the relative absence of introns in the genomes of most modern prokaryotes (Koonin 2006). Of course, this could also be a case of prokaryotes using viruses to store these elements, until needed. In either instance, introns were donated and most were not replaced thus insuring that eukaryotes and not prokaryotes would evolve into new species.

That these prokaryotes at one time may have contained an abundance of introns may also account for why the genomes of archae and bacteria contain split genes (Dassa et al., 2007). Therefore, having contributed their introns to the eukaryotic genome, most archae and most bacterial genes lack or have only a few introns, and their genes are encoded as uninterrupted open reading frames. This indicates that the donation of introns was not random, but under precise genetic control, such that their transfer to eukaryotes played a highly regulated role in eukaryotic evolution whereas their deletion from the prokaryotic genome insured that only eukaryotes would continue to evolve.

Bursts of introns appear to have invaded the eukaryotic genome initially and possibly at key points in eukaryotic evolution, such as the origin of animals and prior to the divergence of extant eukaryotic lineages (Carmel et al., 2007). For example, lineages leading to animals seem to have experienced a phase of massive intron invasion early in their evolution (Carmel et al., 2007).

After billions, or hundreds of millions or tens of millions of years of stasis, armies of introns either invade or rapidly duplicate within the eukaryotic genome, and are directly associated with, or may have directly triggered bursts of branching speciation and explosions of evolutionary change in the absence of transitional forms. These bursts of evolutionary development are not consistent with Darwinian notions of "small steps." Rather, there appear to be periods of no change which are punctuated by rapid change; a phenomenon that Eldredge and Gould (1972; Gould 2002) described as "punctuated equilibrium." Indeed, there is no fossil evidence of gradual change from one species to another or any fossil record of transitional forms acting as an evolutionary bridge between species (Eldredge and Gould 1972; Gould 2002). Evolution occurs in leaps. Thus, the regulation and coordination of these great evolutionary leaps may well be yet another function of introns acting on genes which then express precoded traits.

Although the position of an intron in a gene's coding sequence is well conserved, introns can make copies of themselves which can be snipped out and transposed to another region of the genome (Finnegan, 1989; Moran et al., 1999). Introns change position within the genome, acting as a viral retrosposons and transposable elements. Moreover, they can hitch a ride on a plasmid, and invade and transpose themselves into the genomes of cospecies (Dujon, 1989; Dujon et al., 1989; McDonald 1993). In this manner, they can coordinate gene expression among most members of the same species, such that all make the same evolutionary leaps simultaneously.

Also many drop out of the genome after serving their function, which in turn would effect gene selection and exon transcription. When introns drop out, their deletion may halt any further evolutionary advance, thus leading to another long period of stasis. They may also trigger the extinction of speices. Thus when introns are gained, there may follow bursts of evolutionary change and the emergence of species which had never before been seen on Earth.

It is precisely when new species emerge that introns may be acquired, change position, and activated or silence new gene sequences, and in this regard, the intron, as transposable element, is acting like a virus. In fact, transposable retroelements are not simply derived from viruses, but new waves of elements are inserted after new species evolve. Thus, viral elements already within the genome may trigger speciation which enables viruses-in-wating, to insert DNA, RNA, and additional regulatory elements. Until specific hosts evolve, the targeting virus may remain inactive. Therefore, considerable highly regulated coordinated activity characterizes these interactions. That is, virus trigger the evolution of new species which are invaded by viruses-in-waiting.

Viruses, including retroviruses target specific hosts and often specific cells and tissues. The DNA or RNA inserted may or may not be transcribed but may remain silent. Endogenous retroviruses, by incorporating into the germ line, can be past down to subsequent generations and species, and then, in response to specific genetic-environmental changes, become highly active. Once activated, they proliferate and transpose throughout the genome, effecting gene regulation and expression, and in so doing, they may trigger the metamorphosis of host species which yet other viruses may then invade.

Flurries of ERV activity, invasions, proliferation, deletions, and extinctions have corresponded to the divergence and metamorphosis of numerous species, and are associated with the Cambrian Explosion 540 million years ago, including the evolution of jawed vertebrates (Agrawal et al. 1998, Kapitonov & Jurka 2005), the subsequent split between fish and tetrapods 450 mya (Volff et al. 2003), the giant leap from teleost fish to amphibians 350 mya (Volff et al. 2001c), then reptiles (Hude et al., 2002) and leading up to birds, mammals (Herniou et al., 1998) then primates and humans (Hughes and Coffin 2001; Sverdlov 2000). Genes have been turned on and off, genes have been split, different sequences of exons have been activated or silenced, and genes have been combined and then expressed giving rise to quantum leaps in evolutionary metamorphosis, and every stage is linked to viral activity. In fact, viruses may transfer genes and introns from species to species, thus insuring that some species evolve and that other remain in stasis.

For example, retroelements were transferred from reptiles to mammals using poxviruses (Piskurek & Okada 2007). This invasion led to the formation of many mammalian genes via the activity of retrotranspons which in turn created families of genes which were repeatedly duplicated by at least five independent molecular events (Campillos et al. 2006). From mammals there followed the metamorphosis of primates which were targeted by additional viral invasions and gene insertions coupled with flurries of retro-activity proceeded by ERV extinctions.

For example, with the evolution of monkeys, 55 mya, ERVs formed numerous proviruses which became highly active and increased their activity until the divergence of Old World and New World primates (Lavie et al., 2004). However, there is no trace of ERV activity in prosimians. In addition, following the split between New and Old World monkeys 30 to 35 mya, new classes of ERVs flourished (Mayer and Meese 2002; Mayer et al., 1998; Medstrand and Mager 1998; Medstrand et al., 1997; Seifarth et al., 1998; Sverdlov 2000). During a period of ape-primate proliferation from 15 mya to 6 mya ERVs were again repeatedly mobilized (L�pez-S�nchez et al., 2005), with extensive traces being retained even in the human genome. There followed yet another period of ERV proliferation 8 to 6 MYA (Barbulescu et al., 1999; Johnson and Coffin 1999; L�pez-S�nchez et al., 2005) corresponding with the divergence between the common ancestors for chimps and humans, and then many of the ERV families became inactive and went extinct (L�pez-S�nchez et al., 2005).

Yet other ERV families have lived for tens of millions of years, continuing in the primate lineage leading to humans and displaying periodic bursts of activity which continued after the human-chimpanzee split (Costas 2001; Mayer et al., 1998; Medstrand and Mager 1998; Reus et al., 2001). However, hundreds of retrogenes were also formed in both the chimpanzee and human lineages after they split from a common ancestor (Chimpanzee Sequencing and Analysis Consortium 2005). Yet others are unique to humans and continue to show activity (Barbulescu et al., 1999; Buzdin et al., 2003; Medstrand and Mager 1998), and have contributed to human genetic diversity (Seleme et al. 2006) and the evolution of numerous species Homo.

Thus we see a leaping, progressive pattern of speciation and primate-human evolution where viral elements exert major influences on the genome, leading to new primate-human species which are invaded by yet other viral elements, including waves of group II introns and retrosponsons. These events are accompanied by deletions and duplications which are also species specific. For example, comparisons of gene content between macaque, human and chimpanzee genomes (Hahn et al., 2007) support an overall increase in duplication activity in the common ancestor of chimpanzees and humans compared with other mammals. In addition, human duplications are genetically more diverse when compared with chimpanzee duplications (Cheng et al., 2005).

Further, once a new species has been genetically manufactured, many of these viral elements become inactive or they are deleted from the genome of subsequent species. For example, hundreds of deletions took place independently in chimpanzee and human lineages after divergence from their last common ancestor (Sen et al. 2006, Han et al. 2007). There is evidence for an almost twofold increase in gene loss in humans and chimpanzees when compared with macaques, and an almost fourfold increase in contrast to other mammals including dogs, mice and rats (Hahn et al., 2007; Rhesus Macaque Genome Sequencing and Analysis Consortium, et al., 2007; Wang et al., 2006).

Endogenous retroviruses, therefore, have profoundly affected the genomes of numerous species in the evolutionary lineage leading to Homo sapiens (Mayer and Meese 2005) and several ERV families are still active in present-day humans (Belshaw et al., 2005; L�wer et al., 1993; Medstrand and Mager 1998). Genome sequencing reveals that 8% of the human genome consists of human endogenous retroviruses (HERVs), and, if we extend this to HERV fragments and derivatives, the retroviral legacy amounts to roughly half our DNA (Bannert and Kurth 2005; Medstrand et al., 2002).

Human evolution, therefore, has been shaped by successive waves of viral invasion (Sverdlov 2000) which have induced large-scale deletions, duplications and chromosome reshuffling in the human genomic and have been a major source of genetic diversity (Hughes and Coffin 2004). In fact, about one quarter of all analyzed human promoter regions harbor sequences derived from viral elements (Jordan et al. 2003)

Human evolution, and the evolution of all species can also be traced backward in time to a period around 4 billion years ago, when archae and bacteria donated genes which were combined to generate the first Earthly multi-cellular eukaryotes. These genes interact with viral regulatory genes, introns, and proteins, in a lock and key, coordinated fashion, and eukaryotes became more complex and their genome repeatedly duplicated in size.

These viral invasions and prokarotic genetic contributions to the evolution of eukaryotes leading to humans should not be viewed as agents of chance. Rather, viruses, prokaryotes, and eukaryotes, constitute a genetic super-organism and the transfer of viral elements and the activation vs silencing of genes has been under precise genetic regulatory control. Further, there has been a progressive, step-wise sequential order to these viral invasions and gene activations, silencing, and deletions, and different host organisms have "evolved" accordingly.

Viruses are host specific and thus in order to invade, or to become activated, requires the manufacture of specific hosts species--and this too has taken place in a progressive highly regulated manner through the activation of genes which express precoded traits.

For example, most of the ERV sequences in the human genome are primate-specific (Sverdlov, 2000) and code for specific organs and tissues, such as the brain. However, they act on genes whose heritages extends backwards in time to prokarotes. Thus most human genes are ancient, have been highly conserved, and share orthologs with distantly related species. Hence, there is a specific interaction between introns and ancient genes which had been passed down for hundreds of millions if not billions of years, albeit in silent form. These ancient genes are subsequently activated by viral genes, introns, transposons, and promoters which selectively target these ancient genes within specific hosts species, thereby triggering episodes of speciation. Again, each viral key had to await the evolution of a specific genetic lock and once that lock evolved, the key was inserted opening the door to the next stage in evolutionary metamorphosis.

It must be stressed, however, that genes act on the environment, biologically altering the biosphere, and that the altered environment also acts on gene selection. Hence, evolution of Earth is the result of the interactions of prokaryotic and viral elements, which act on genes transferred to the eukaryotic genome by prokarotes and viruses, and which act on the environment, which acts on gene selection, such that species emerge into a world which has been biologically prepared for them.

Many of these genes, including those inserted by viruses, are held in abeyance until the biosphere has been altered in specific ways, and until specific hosts evolve; at which point viruses may invade and insert genes which interact with ancient genes which had been donated by prokaryotes hundreds of millions if not billions of years before. These speciation events are often preceded or proceeded by additional invasions such that species diverge from common ancestors only to be invaded by yet another wave of viral elements when new hosts evolve.

GENES BIOLOGICALLY MODIFY THE ENVIORNMENT WHICH ACTS ON GENE SELECTION

Genes often interact in networks which change the environment and which are influenced by the changing environment. Change the environment and gene expression patterns may be altered, giving rise to slight or major differences in the products produced and allowing for the expression of pre-determined traits (Rutherford & Lindquist, 1998). For example, genes may be silenced via protein buffers which wrap around and isolated them from triggering mechanisms be then environmental or genetic. These inhibitory mechanisms may include heterochromatin or methyl groups which reduced the expression of specific genes and gene networks via DNA methylation. These inhibitory buffers prevent the expression of signal-transduction proteins. However, if the environment is significantly altered, these inhibitory mechanisms may be nullified and silent functions precoded into these silent genes will be expressed.

As demonstrated by experiments performed by Rutherford and Lindquist, (1998) when these suppressive protein-buffering actions are altered by environmental change, including temperature fluctuations, "variants are expressed and selection can lead to the continued expression of these traits, even when" the actions of these repressor proteins are restored.

However, biological organisms have been largely responsible for many of the most dramatic changes in the climate and global temperatures over the history of this planet (Joseph 2009d). Genes effect the environment such as through the release of oxygen, calcium and other products which build up and gene selection, creating an interactive feedback loop which significantly impacts the speed and rate of evolutionary metamorphosis. In order for these repressor proteins and other regulating genetic mechanisms to be switched off or on, requires contact and exposure to specific environmental agents such as oxygen and calicum, both of which are produced biologically.

Thus, what has been described as a random evolution, is in fact under the interactive control of genetic and biologically altered environmental influences which directly impact genetic mechanisms involved in gene silencing, gene duplication, and gene expression, thereby giving rise to traits, functions, organs, and species, which had been precoded into silent genes inherited from ancestral species. These genes and regulatory elements were donated to the eukaryotic genome by viruses and prokaryotes--the ancestors of which, arrived on Earth from other, more ancient worlds.

Evolution is not random. Evolution is embrogenesis and metamorphosis: The replication of life forms which long ago lived on other planets.

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