The origin of biological homochirality along with the origin of life

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.</div

Events occurring in the model and their associated probabilities.

<p>Solid arrows represent chemical events and dashed arrows represent other events. (<b>a</b>) The events occurring in a grid room. Legends: Np, nucleotide precursor; Nt, nucleotide (A, U, C, or G); Ap, amphiphile precursor; Am, amphiphile. This version is for the true-protocell system. For the pseudo-protocell system, the events concerning Asr would not occur. For the naked system, the events concerning amphiphilic molecules and their precursors would not occur; there is no membrane at the edge of the grid room; nucleotides and RNA may also move to an adjacent grid room (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035454#pone-0035454-t001" target="_blank">Table 1</a>, note b). (<b>b</b>) Events concerning the behaviors of the protocells. When a protocell move to an adjacent (top, down, left, or right) naked grid room, the protocell would push away molecules in that room. When a protocell divides, amphiphiles on the membrane and molecules in the protocells would be distributed randomly between the two offspring protocells. One of the offspring protocells would occupy an adjacent naked grid room and push away molecules in that room.</p

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

PAT = 0 (i.e., template-directed synthesis is disabled); PRL = 1×10−6, PNDE = 1×10−5, FCSS = 0. The extending rate for a monomer, dimmer, trimmer and longer polymer is represented as R1-mer, R2-mer, R3-mer, and Rn-mer, respectively (PRL is multiplied by one of such rates in the corresponding situation). Dotted line (control): Rn-mer = R3-mer = R2-mer = R1-mer (the dotted line actually overlaps with the dashed-dotted line, which are both at the level of ee = 0); dash-dotted line: Rn-mer = R3-mer = 5×R2-mer = 50×R1-mer (the primer effect is not sufficiently strong to induce the chirality-deviation); dashed line: Rn-mer = R3-mer = 10×R2-mer = 100×R1-mer (the primer effect is strong enough to induce a chirality-deviation); solid line: Rn-mer = R3-mer = 20×R2-mer = 200×R1-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.</p

Parameters used in the computer simulation.

Parameters used in the computer simulation.</p

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., PTLR = 0). About the primer effect in surface-mediated synthesis: Rn-mer = R3-mer = 2×R2-mer = 20×R1-mer (PRL 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: Rn-mer = R3-mer = 2×R2-mer = 10×R1-mer (PTL 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., PNFR = 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).</p

Co-spread of the ribozymes (the color-coded legends have been explained in detail in the following).

<p>The characteristic domain for a ribozyme or the control RNA species is a stem-loop “X₃X₂X₁LLLLY₁Y₂Y₃”, in which an “L” denotes a nucleotide in the loop, whereas the nucleotides in the stem, X₁, X₂, and X₃ are complementary (by Watson-Crick pairs or a G-U pair) to Y₁, Y₂, and Y₃, respectively. The loop nucleotides are “AGUC” for Rep (red stars), “ACUG” for Nsr (green stars), “AUCG” for Asr (blue stars), and “UCAG” for the control (triangles). Nucleotide precursors (dots) are represented in a 1/200 scale relative to the number of the ribozymes (e.g., 400 denotes 8×10⁴). The parameter values have been listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035454#pone-0035454-t001" target="_blank">Table 1</a>. For the naked stage (<b>a</b>), 10 grid rooms, chosen randomly, were each inoculated with five molecules of Rep, Nsr and the control at step 1×10⁴ (cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035454#pone-0035454-g004" target="_blank">Fig. 4a</a>); “x-shapes” show the tendency change of Rep (red) and Nsr (green) when <i>PMV</i> was enlarged to 0.01 (originally 5×10⁻⁴) at step 2×10⁶. For the pseudo-protocell substage (<b>b</b>) and the true-protocell substage (<b>c</b>), 10 grid rooms, chosen randomly, were each inoculated with an empty protocell at step 1×10³; ten grid rooms, chosen randomly, were each inoculated with an protocell containing five molecules of the ribozymes (Rep and Nsr in <b>b</b>, plus Asr in <b>c</b>) and the control at step 1×10⁴ (cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035454#pone-0035454-g004" target="_blank">Fig. 4b and c</a>). Black circles represent total protocells. Other circles represent protocells containing Rep, Nsr and Asr (orange); Rep and Nsr but not Asr (yellow); Rep and Asr but not Nsr (magenta); Nsr and Asr but not Rep (cyan); only Rep (red); only Nsr (green); and only Asr (blue).</p

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 PMN 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.</p

Influence of the parameters on the spreading chance of the ribozymes (part 2).

<p>The interpretation of this figure is the same as that of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035454#pone-0035454-g005" target="_blank">Fig. 5</a>. (<b>a</b>) The naked stage. (<b>b</b>) The pseudo-protocell substage. (<b>c</b>) The true-protocell substage. The parameters in the top panels of <b>b</b> and <b>c</b> are parallel to those in <b>a</b>, whereas the parameters in the bottom panels of <b>b</b> and <b>c</b> are those only affecting the protocell stage.</p

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.</p

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. PTL = 0.01. (a) 50 molecules of D-RNA, 6 nt in length, are inoculated at 1×106 step. PRL = 0 (i.e., de novo appearance of RNA is impossible). Solid line: FCST = 0 (complete chiral-selection); dashed line: FCST = 0.5 (partial chiral-selection); Dash-dotted line: FCST = 1 (no chiral-selection). See S2 Fig for the cases corresponding to more FCST values. The dotted line represents the case in which neither chiral-selection nor cross-inhibition termination exists. (b) RNAs appear de novo. PRL = 1×10−6, FCST = 0.5, FCSS = 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.</p