1. Life on Earth

Is life on Earth a unique entity in the universe or is it ubiquitous? Recent astronomical studies have shown that more than 5% of the solar-type stars investigated thus far have gas giant planets like Jupiter (Ida and Lin, 2004). The core accretion model indicates that both gas giant planets and terrestrial planets are formed through the same processes (Mizuno, 1980; Bodenheimer and Pollack, 1986), suggesting that terrestrial planets are not rare entities in the universe (Ida and Lin, 2004). If the mass of a terrestrial planet is more than that of Mars, its gravity is sufficient to retain atmosphere. In addition, if such a planet is placed around a fixed star at a suitable orbital radius, liquid water (oceans) may be maintained on its surface. A super-Earth orbiting a low-mass star, with a planetary mass and radius consistent with a composition primarily of water and with an atmosphere, has recently been discovered (Charbonneau et al., 2009). A computer-simulation analysis based on the standard model of planetary system formation indicates that more than 10% of solar-type stars in our galaxy are orbited by habitable planets, like Earth (Ida, 2005).

The existence of oceans is a key requirement for the emergence of life. Thus, since planets similar to Earth exist outside this solar system, and given the discovery of an ocean covered super-Earth, then life may exist on innumerable other planets in the universe. However, life has not yet been detected on any other planet.

The reason why carbon is the fundamental element in all living beings could be elucidated by comparing the abundance of various elements in the universe. The most abundant element is hydrogen, which makes up approximately 70% of all matter, followed by helium (28.0%), oxygen (0.92%), carbon (0.34%), and nitrogen (0.12%) (Croswell, 1996). It is reasonable to assume that terrestrial life mainly contain the above elements, which are highly prevalent in the universe (H, O, C, and N); helium is not present in living beings because it is a stable and inactive element.

Carbon tends to form 4 covalent bonds, resulting in the formation of many types of molecules with various activities, functions, lengths, and conformations. Silicon mainly exists as silicates in Earth’s crust and is 135 times more abundant than carbon anywhere on Earth.

In addition, like carbon, silicon has the ability to form 4 covalent bonds. However, unlike the stable C-C bonds, Si-Si bonds are susceptible to the action of H₂O, NH₃⁺, and O₂ (Fox, 2004). Furthermore, the structural flexibility of silicon compounds is much lower than that of carbon compounds. The transformation of silicon-compounds usually requires high temperature and pressure.

Crick and Orgel (1973), Hoyle and Wickramasinghe (2000), and Joseph (2009) have all developed elaborate panspermia models to explain the extra-terrestrial origins of life on Earth. According to these theories, the first life forms on Earth came from outer space. Joseph (2009) and Hoyle and Wickramasinghe (2000) propose that life may hitchhike across galaxies embedded in comets, meteors and planetary debris. In Joseph's (2009) widely debated model, life-bearing planets were ejected from a "parent star" a billion years before supernova, and these rogue planets, and planetary debris with life inside, formed part of this solar system. Joseph points to evidence of past life on Mars, which appeared around the same time as life on Earth, as additional evidence for his theory. Although the Mars dated was attacked soon after it was published, a recent reexamination of the ALH84001 meteorite provides convincing evidence that life may have existed on ancient Mars (Thomas-Keprta et al., 2009).

Although life may have first originated on other planets only to be deposited on Earth, panspermia models do not explain how life began. Numerous scientists have been attempting to answer this question.

Miller (1953) carried out a discharge experiment using a putative primitive atmosphere, and the synthesis of several amino acids occurred during this experiment. However, the mechanism underlying the organization of these molecules as the "building blocks" of life remains unclear. Simple "organic" compounds must have elongated to form organized molecular systems, which were probably the primordial first "life forms" either on Earth or some other planet. Modern biological systems consist of macromolecules such as proteins, DNA, and RNA. DNA and RNA contain phosphorus atoms. Since the amount of phosphorus in sea water is small and because the flow of energy was required for the polymerization of small molecules on primitive Earth, nucleic acids may have originated in areas other than the sea.

It has been suggested that unusual bombardments of meteorites ca. 4 billion years ago resulted in the accumulation of molecules in the soil and was a significant event in the generation of the "building blocks" of life on Earth (Furukawa et al., 2009).

2. Homochirality is Necessary for Life

Homochirality was crucial for the organization of biomolecules. Chiral molecules are molecules that cannot be superposed on their own mirror image. Proteins and nucleic acids (DNA and RNA), the 2 main types of biomolecules, have chiral structures. Natural proteins comprise α-amino acids that are exclusively left-handed (L-amino acids), whereas DNA and RNA possess right-handed sugars (D-deoxyribose and D-ribose, respectively). Thus, the biological system is "homochiral." Tertiary structures of proteins are formed by appropriate folding of secondary structures such as α-helices and β-sheets. α-helices and most β-sheets configurations can form only if the amino acids in the involved proteins are homochiral, i.e., they are all L-amino acids or D-amino acids (Bonner, 2000).

The elongation of RNA (nucleotide chains) is believed to be a crucial event for the organization of life, and chiral selection has been observed during template-directed oligomerization of nucleotides. Oligomerization occurs when the monomers are of the same optical handedness as the template (Joyce et al., 1984). In addition, all possible combinations of homo- and hetero-chiral diastereomers of short RNA yield chiroselective all left-handed or all right-handed products during template-directed auto-oligomerization (Bolli et al., 1997). Thus, homochirality in biomolecules is the result of the chemical features of the building blocks.

Then, the question arises, why are natural proteins composed of L-amino acids, and not D-amino acids? This is one of the most important questions in biology, and no clear answer has been found, despite extensive research. Physicists and chemists have formulated various hypotheses based on different standpoints. The discovery of parity violation during the β-decay of nuclei has led to the conclusion that a slight increase in the ratio of L- to D-enantiomers (<10^-11) might have resulted in the formation of an L-amino acid-based biological world (Hegstrom, 1987). In fact, in meteorites, the frequency of L-amino acids is only slightly greater than that of D-amino acids (Oró, 1961; Chyba et al., 1990; Chyba and Sagan, 1992). Polarized synchrotron radiation from neutron stars may have affected the proportions of these 2 enantiomers (Bonner, 1996). Furthermore, enantioselective autocatalysis by chiral materials has been reported (Soai et al., 1995; Blackmond, 2004; Kawasaki et al., 2009). However, the excess of L-enantiomers is very slight and may not have had any effect on the evolution of biological systems, though the contribution of this excess cannot be completely ruled out.

3. RNA World and tRNA Aminoacylation

The discovery of ribozymes (Kruger et al., 1982; Guerrier-Takada et al., 1983) has changed the concept of the origin of life. The fact that RNA acts as both an information carrier and a catalyst, led Gilbert (1986) to coin the term "RNA world," which may have existed during the initial stages of the formation of life.

The key step in understanding the evolution from the putative RNA world to the "protein world" is the "encounter" of RNA with amino acids, which are the components of proteins; this encounter corresponds to the process of tRNA aminoacylation (Figure 1). During modern protein biosynthesis, cognate amino acids are attached to a specific tRNA by protein enzymes called aminoacyl-tRNA synthetases (Schimmel, 1987). Therefore, the origin of amino acid homochirality should be considered from the standpoint of tRNA aminoacylation.

tRNA synthetases catalyze tRNA aminoacylation primarily in 2 consecutive steps: amino acid activation and amino acid transfer to tRNA. According to the RNA world hypothesis, tRNA aminoacylation may have been performed without proteins. Aminoacyl adenylate, the reaction intermediate of the current aminoacylation by tRNA synthetases, is an activated form of an amino acid, and this molecule is known to be formed under abiotic conditions (Paecht-Horowitz and Katchalsky, 1973). This, when considered together with the fact that oligonucleotides could have been produced prebiotically (Lohrmann et al., 1980), suggests that aminoacyl phosphate oligonucleotides may have existed during the early era of Earth if life in fact began on this planet.

All biological systems are believed to contain L-shaped tRNAs. One arm of the L-shaped of tRNA is called a "minihelix" and is thought to be the primordial part. This arm can be the substrate for tRNA synthetases. Minihelices are believed to have evolved to L-shaped tRNAs by the addition of another arm (including anticodon); this change was accompanied by an increase in the accuracy of the tRNA aminoacylation and the mRNA decoding system (Schimmel et al., 1993; Schimmel and Ribas de Pouplana, 1995) (Figure 1).

4. Chiral-Selective Aminoacylation of RNA

The above observations indicate that primordial tRNAs (minihelices) could have been non-enzymatically aminoacylated by aminoacyl phosphate oligonucleotides. Non-enzymatic aminoacylation of minihelices can be accomplished by placing these compounds in close proximity to high-energy amino acid donors (aminoacyl phosphate oligonucleotides). The change in free energy during aminoacyl phosphate hydrolysis is greater than that during aminoacyl ester hydrolysis; therefore, aminoacyl transfer from the 5′-phosphate moiety of the oligonucleotide to the minihelix is a "downhill" reaction. The universal CCA sequence at the 3′-end of the minihelix and an aminoacyl phosphate oligonucleotide are bridged by another oligonucleotide when the former 2 compounds are in close proximity to each other (Figure 1). This results in adequate chiroselective aminoacylation of the minihelix (L-amino acid preference) and a specificity for the 3′-OH as the aminoacylation site (Tamura and Schimmel, 2004). This preference is sufficient basis for the formation of homochiral proteins during evolutionary processes. Chiroselectivity depends on the structural features of the chiral molecules involved. In fact, an experiment conducted in a "mirror world" by using L-ribose RNAs showed opposite results, i.e., a preference for D-amino acids (Tamura and Schimmel, 2004). The main reason for chiroselectivity is steric clash of the side chains of D-amino acids with the nearby 3′-OH of the terminal adenosine of the minihelix. In contrast, the side chain of L-amino acids is located distal to the 3′-OH (Tamura and Schimmel, 2006; Tamura, 2008; Tamura, 2009).

5. Origin of Amino Acid Homochirality

Despite some limitations, the RNA world hypothesis (Gilbert, 1986) has provided a reasonable explanation to the classic "chicken-or-egg" conundrum in regards to biological molecules--what came first, nucleic acids or proteins?

The RNA world is believed to have existed during the early stages of biological evolution. Repeated oligomerization of short nucleotides would have been the main pathway of RNA elongation. During this step, the elongated products may have been homochiral--all L- or D-products (Bolli et al., 1997). These putative homochiral RNAs formed from short oligomers may not have had identical sequences. Although the numbers of the potential sequences is in the order of 4ⁿ (where n is the number of nucleotides), the number of sequences actually formed during RNA lengthening was much smaller. If RNA had been elongated to a length similar to that of modern tRNA (~75 nucleotides), the total mass of all the potential molecules would be one-hundredth of the total mass of the Earth. Therefore, as RNA elongation continued further, symmetry violation must have occurred as a matter of course. One of the 2 possible sequences would have occurred in only D-libraries and the other, in only L-libraries.

A specific sequence that incidentally exhibited an important chemical characteristic required for the establishment of the RNA world may have been present only in the D-libraries, and this might have led to the origin of a homochiral RNA world. In this case, L-amino acids would have been selected through non-enzymatic aminoacylation of primordial RNA, leading to the synthesis of homochiral (L) natural proteins (Tamura, 2008, 2009) (Figure 1).

Homochirality is probably a result of the evolution of life on Earth. If the proponents of panspermia are correct, life may not be limited to this planet (Crick and Orgel, 1973; Hoyle and Wickramasinghe, 2000; Joseph 2009). Although it has been argued that panspermia does away with the need for abiotic explanations for life on Earth, the converse could also be said; abiogenesis makes panspermia unnecessary. Regardless of the mechanisms of life dispersal, life had to have a beginning. Even if deposited on another world, or created abiotically on other worlds, we could assume that many of the elements in the living beings on other planets would be similar to those on Earth; carbon would be the critical element of these life forms--though this is not to say that throughout the cosmos all life forms must be like those of Earth. However, without evidence of non-carbon based life, then the concept of homochirality is a crucial issue related to the origin and evolution of life in the universe. Non-enzymatic aminoacylation of RNA minihelices by aminoacyl phosphate oligunucleotides is a key event that determined the chiral preference for L-amino acids over D-amino acids (Tamura and Schimmel, 2004). The structural and chemical features of the primitive molecules enabled these molecules to detect the chirality of other molecules.

Acknowledgements I would like to thank Professor Paul Schimmel (The Scripps Research Institute) for encouragement and discussions on this study. This work was supported by a grant from PRESTO (RNA and Biofunctions), Japan Science and Technology Agency, Japan.