Evolution of the genetic code: partial optimization of a random code for robustness to translation error in a rugged fitness landscape.
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It has been repeatedly argued that this structure of the code results from selective optimization for robustness to translation errors such that translational misreading has the minimal adverse effect.The properties of the standard code were compared to the properties of four sets of codes, namely, purely random codes, random codes that are more robust than the standard code, and two sets of codes that resulted from optimization of the first two sets.The reason the code is not fully optimized could be the trade-off between the beneficial effect of increasing robustness to translation errors and the deleterious effect of codon series reassignment that becomes increasingly severe with growing complexity of the evolving system.
Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. novozhil@ncbi.nlm.nih.gov
ABSTRACT
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Background: The standard genetic code table has a distinctly non-random structure, with similar amino acids often encoded by codons series that differ by a single nucleotide substitution, typically, in the third or the first position of the codon. It has been repeatedly argued that this structure of the code results from selective optimization for robustness to translation errors such that translational misreading has the minimal adverse effect. Indeed, it has been shown in several studies that the standard code is more robust than a substantial majority of random codes. However, it remains unclear how much evolution the standard code underwent, what is the level of optimization, and what is the likely starting point. Results: We explored possible evolutionary trajectories of the genetic code within a limited domain of the vast space of possible codes. Only those codes were analyzed for robustness to translation error that possess the same block structure and the same degree of degeneracy as the standard code. This choice of a small part of the vast space of possible codes is based on the notion that the block structure of the standard code is a consequence of the structure of the complex between the cognate tRNA and the codon in mRNA where the third base of the codon plays a minimum role as a specificity determinant. Within this part of the fitness landscape, a simple evolutionary algorithm, with elementary evolutionary steps comprising swaps of four-codon or two-codon series, was employed to investigate the optimization of codes for the maximum attainable robustness. The properties of the standard code were compared to the properties of four sets of codes, namely, purely random codes, random codes that are more robust than the standard code, and two sets of codes that resulted from optimization of the first two sets. The comparison of these sets of codes with the standard code and its locally optimized version showed that, on average, optimization of random codes yielded evolutionary trajectories that converged at the same level of robustness to translation errors as the optimization path of the standard code; however, the standard code required considerably fewer steps to reach that level than an average random code. When evolution starts from random codes whose fitness is comparable to that of the standard code, they typically reach much higher level of optimization than the standard code, i.e., the standard code is much closer to its local minimum (fitness peak) than most of the random codes with similar levels of robustness. Thus, the standard genetic code appears to be a point on an evolutionary trajectory from a random point (code) about half the way to the summit of the local peak. The fitness landscape of code evolution appears to be extremely rugged, containing numerous peaks with a broad distribution of heights, and the standard code is relatively unremarkable, being located on the slope of a moderate-height peak. Conclusion: The standard code appears to be the result of partial optimization of a random code for robustness to errors of translation. The reason the code is not fully optimized could be the trade-off between the beneficial effect of increasing robustness to translation errors and the deleterious effect of codon series reassignment that becomes increasingly severe with growing complexity of the evolving system. Thus, evolution of the code can be represented as a combination of adaptation and frozen accident. |
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Mentions: We further examined the length of the evolutionary path to convergence (on a locally optimized code) measured as the number of pairwise swaps that are required to reach the minimum error cost (Figs. 7, 8). For a random code to reach its local minimum, when the PRS is used, 19 swaps are necessary on average (Fig. 7b), and the maximum number of swaps among the 300 tested codes was 30; for the Gilis matrix, the corresponding numbers were 17 and 28 swaps (Fig. 8b). The standard code reached the local minimum after 9 and 11 swaps for the PRS and the Gilis matrix, respectively, which is significantly fewer than the means for the random codes (Figs. 7b, 8b). Notably, on average, the random codes reached, at convergence, the same level of robustness as the standard code although the latter required fewer steps to get there (Figs. 7a, 8a). Put another way, it takes a random code, on average, 8 or 7 swaps (depending on the matrix) to reach the robustness level of the standard code and, then, another 11 or 10 steps to reach the local minimum. Thus, these results supported the notion that the standard genetic code is a partially optimized random code and suggest that it had gone about half of the way along a typical optimization path. We then examined the optimization paths of random codes with a fitness greater than that of the standard code and found that a substantial fraction of these (Figs. 7cd and 8cd) converged at much higher levels of robustness (higher fitness peaks) than the standard code. Again, this result emphasizes the "mediocrity" of the standard code. |
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Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. novozhil@ncbi.nlm.nih.gov
Background: The standard genetic code table has a distinctly non-random structure, with similar amino acids often encoded by codons series that differ by a single nucleotide substitution, typically, in the third or the first position of the codon. It has been repeatedly argued that this structure of the code results from selective optimization for robustness to translation errors such that translational misreading has the minimal adverse effect. Indeed, it has been shown in several studies that the standard code is more robust than a substantial majority of random codes. However, it remains unclear how much evolution the standard code underwent, what is the level of optimization, and what is the likely starting point.
Results: We explored possible evolutionary trajectories of the genetic code within a limited domain of the vast space of possible codes. Only those codes were analyzed for robustness to translation error that possess the same block structure and the same degree of degeneracy as the standard code. This choice of a small part of the vast space of possible codes is based on the notion that the block structure of the standard code is a consequence of the structure of the complex between the cognate tRNA and the codon in mRNA where the third base of the codon plays a minimum role as a specificity determinant. Within this part of the fitness landscape, a simple evolutionary algorithm, with elementary evolutionary steps comprising swaps of four-codon or two-codon series, was employed to investigate the optimization of codes for the maximum attainable robustness. The properties of the standard code were compared to the properties of four sets of codes, namely, purely random codes, random codes that are more robust than the standard code, and two sets of codes that resulted from optimization of the first two sets. The comparison of these sets of codes with the standard code and its locally optimized version showed that, on average, optimization of random codes yielded evolutionary trajectories that converged at the same level of robustness to translation errors as the optimization path of the standard code; however, the standard code required considerably fewer steps to reach that level than an average random code. When evolution starts from random codes whose fitness is comparable to that of the standard code, they typically reach much higher level of optimization than the standard code, i.e., the standard code is much closer to its local minimum (fitness peak) than most of the random codes with similar levels of robustness. Thus, the standard genetic code appears to be a point on an evolutionary trajectory from a random point (code) about half the way to the summit of the local peak. The fitness landscape of code evolution appears to be extremely rugged, containing numerous peaks with a broad distribution of heights, and the standard code is relatively unremarkable, being located on the slope of a moderate-height peak.
Conclusion: The standard code appears to be the result of partial optimization of a random code for robustness to errors of translation. The reason the code is not fully optimized could be the trade-off between the beneficial effect of increasing robustness to translation errors and the deleterious effect of codon series reassignment that becomes increasingly severe with growing complexity of the evolving system. Thus, evolution of the code can be represented as a combination of adaptation and frozen accident.