The origin of biological homochirality along with the origin of life

Abstract

How homochirality concerning biopolymers (DNA/RNA/proteins) could have originally occurred (i.e., arisen from a non-life chemical world, which tended to be chirality-symmetric) is a long-standing scientific puzzle. For many years, people have focused on exploring plausible physic-chemical mechanisms that may have led to prebiotic environments biased to one chiral type of monomers (e.g., D-nucleotides against L-nucleotides; L-amino-acids against D-amino-acids)-which should have then assembled into corresponding polymers with homochirality, but as yet have achieved no convincing advance. Here we show, by computer simulation-with a model based on the RNA world scenario, that the biased-chirality may have been established at polymer level instead, just deriving from a racemic mixture of monomers (i.e., equally with the two chiral types). In other words, the results suggest that the homochirality may have originated along with the advent of biopolymers during the origin of life, rather than somehow at the level of monomers before the origin of life.

Fig 1. The arising of homochirality at the polymer level in the RNA world.

The evolution starts with a racemic pool of nucleotide precursors, in which the two chiral types can interconvert readily (the green star). RNA’s preference to incorporate monomers of chirality identical to its own (‘chiral selection’) in its de novo polymerization (the surface-mediated synthesis) and replication (the template-directed synthesis) brings about the autocatalytic feature, which may amplify the slight difference between the two chiral forms–perhaps initially occurring by chance. During the amplification, the materials in the opposite form shift toward the target form through the racemization-balancing (the green star). Consequently, substantial chirality-deviation of the whole system would occur (the green arrow), engendering long RNA chains with uniform handedness, which renders the appearance of ribozymes possible. Then, the advent of ribozymes (see text for explanations of such ribozymes), may further enhance the chirality-deviation, due to their more specific, efficient chiral-selection. That is, the resulted biological chirality of one type, instead of the other type, should have initially occurred by chance this way.

Fig 2. Chirality-deviation may result from the template-directed synthesis.

Color legends: Red for D-type and blue for L-type (applicable in all figures of the paper). Enantiomeric excess (‘ee’) equals to (D-L)/(D+L), where D and L represent corresponding enantiomers summed up over all the nucleotide precursors, nucleotides and nucleotide residues in RNA within the system. P_TL = 0.01. (a) 50 molecules of D-RNA, 6 nt in length, are inoculated at 1×10⁶ step. P_RL = 0 (i.e., de novo appearance of RNA is impossible). Solid line: F_CST = 0 (complete chiral-selection); dashed line: F_CST = 0.5 (partial chiral-selection); Dash-dotted line: F_CST = 1 (no chiral-selection). See S2 Fig for the cases corresponding to more F_CST values. The dotted line represents the case in which neither chiral-selection nor cross-inhibition termination exists. (b) RNAs appear de novo. P_RL = 1×10⁻⁶, F_CST = 0.5, F_CSS = 0. This is a case in which L-RNA prevails–which is in practice ‘by chance’ (e.g., if using a different random seed in the Monte-Carlo simulation, D-RNA might prevail). The evolution regarding RNA’s chain-length distribution is displayed below, respectively of the two chirality types.

Fig 3. Chirality-deviation may result from surface-mediated synthesis when considering the primer effect.

P_AT = 0 (i.e., template-directed synthesis is disabled); P_RL = 1×10⁻⁶, P_NDE = 1×10⁻⁵, F_CSS = 0. The extending rate for a monomer, dimmer, trimmer and longer polymer is represented as R_1-mer, R_2-mer, R_3-mer, and R_n-mer, respectively (P_RL is multiplied by one of such rates in the corresponding situation). Dotted line (control): R_n-mer = R_3-mer = R_2-mer = R_1-mer (the dotted line actually overlaps with the dashed-dotted line, which are both at the level of ee = 0); dash-dotted line: R_n-mer = R_3-mer = 5×R_2-mer = 50×R_1-mer (the primer effect is not sufficiently strong to induce the chirality-deviation); dashed line: R_n-mer = R_3-mer = 10×R_2-mer = 100×R_1-mer (the primer effect is strong enough to induce a chirality-deviation); solid line: R_n-mer = R_3-mer = 20×R_2-mer = 200×R_1-mer (the primer effect is so strong as to induce a significant chirality-deviation)_. The evolution of RNA’s chain-length distributions for the solid-line case is displayed below (the chains longer than 20 nt are not displayed). Note that the prevailing of D-RNA (instead of L-RNA) as shown in the solid-line case and the dashed-line case is merely by chance.

Fig 4. The emergence of ribozymes in the chirality-deviation background and subsequent enhancement of the chirality-deviation.

(a) The spontaneous appearance of NSR (with a uniform-handedness catalytic domain) in a chirality-deviation background established by the surface-mediated synthesis and the template-directed synthesis, and its effect of augmenting the enantiomeric excess. REP is not considered (i.e., P_TLR = 0). About the primer effect in surface-mediated synthesis: R_n-mer = R_3-mer = 2×R_2-mer = 20×R_1-mer (P_RL is multiplied by one of such rates in corresponding situation; the scale of these rates are generally in accordance with experiments [29,30]; about the primer effect in template-directed synthesis: R_n-mer = R_3-mer = 2×R_2-mer = 10×R_1-mer (P_TL is multiplied by one of such rates in corresponding situation; the scale of these rates are generally in accordance with experiments [27,28]). See Fig 5 and S1 Movie for the evolutionary scenario of this case. (b) The spontaneous appearance of REP (with a uniform-handedness catalytic domain) in a chirality-deviation background established by the surface-mediated synthesis and the template-directed synthesis, and its effect of augmenting the enantiomeric excess. NSR is not considered (i.e., P_NFR = 0). The situation about the primer effects are the same as that assumed in (a). For the panels of chain-length distribution, the chains longer than 20 nt are not displayed. Note that the prevailing of D-RNA and corresponding ribozymes shown in these two cases is merely by chance (i.e., in other cases L-type ones might show up).

Fig 5. Snapshots showing the natural arising of chirality-deviation induced by the surface-mediated synthesis and the template-directed synthesis and subsequent spontaneous emergence of NSR.

Molecules of nucleotides and RNA are represented as solid circles (dots), with diameter in proportion to the square root of the chain-length of these molecules. D-type of nucleotides and RNA are denoted in light red, except for D-NSR, which is denoted in bright red. L-type of nucleotides and RNA are denoted in light blue, except for L-NSR, which is denoted in bright blue (but note: in this case no L-NSR emerges). Step 10,000: after inoculation of nucleotide precursors in the beginning (Step 0), many nucleotide molecules of both chiral types form (tiny dots, see the zoom-in panel); Step 1.2×10⁶: the formation of oligomers of both chiral types; Step 3×10⁶: one chiral type (D-type in this case) achieves superiority, resulting from the surface-mediated synthesis and the template-directed synthesis; Step 4.24×10⁶: the NSR molecule (see the green arrow) which ultimately gives rise to the thriving of NSR in the whole system; Step 4.5×10⁶: the spread of the NSR; Step 6×10⁶: the thriving of the NSR in the whole system. What is displayed in S1 Movie is of the same case, which focuses on the appearance and spread of the NSR (from step 4.2×10⁶ to 4.7×10⁶). See Fig 4A for the evolutionary dynamics of the case.

Fig 6. Events occurring in the modeling system and relevant parameters.

The background is a grid room. Note: besides nucleotides and nucleotide precursors, RNA molecules may also move into the room or outwards (see the two stars), with a probability in positive relation to P_MN but in reverse relation to its chain length (see Methods for details). Theoretically, both D- and L-types of NSR (nucleotide synthetase ribozyme) or those of REP (RNA replicase ribozyme) may occur in the system, and here we only show the D-type ones just for conciseness–corresponding to the cases shown in the results of this paper (Fig 4). Also for simplification, we draw here the surface-mediated synthesis and the template-directed synthesis in a way as if only monomers are able to incorporate, but actually, oligomers may also act as substrates–see Methods for a detailed description of relevant events in the model.