论文标题

稀有事件采样分析发现了遗传密码的健身景观

Rare-Event Sampling Analysis Uncovers the Fitness Landscape of the Genetic Code

论文作者

Omachi, Yuji, Saito, Nen, Furusawa, Chikara

论文摘要

遗传代码是指将64个密码子映射到20个氨基酸的规则。几乎所有生物(除少数例外)都具有相同的遗传代码,即标准遗传密码(SGC)。尽管尚不清楚为什么在进化过程中出现并保持这种通用代码,但可能已在选择压力下保留。比较SGC和数字创建的假设随机遗传代码的理论研究表明,SGC一直承受着强大的选择压力,以使其对转化误差具有牢固的影响。但是,这些先前的研究仅在计算时间的限制中仅在可能的代码空间的一个小子空间中搜索了随机遗传代码。因此,遗传密码的发展方式以及遗传代码适应性景观的特征尚不清楚。通过应用多种统一的蒙特卡洛(一种有效的稀有事件采样方法),我们从遗传代码的更广泛的随机集合中有效地采样了随机代码,估计每10 $ 10^{20} $随机代码中只有一个比SGC更强大。该估计明显小于以前的估计值,其中一个估计值为一百万。我们还表征了具有四个主要健身峰的遗传密码的健身景观,其中之一包括SGC。此外,遗传算法分析表明,在这种多峰的健身景观下的进化可能会以进化路径依赖性方式强烈偏向狭窄的峰。

The genetic code refers to a rule that maps 64 codons to 20 amino acids. Nearly all organisms, with few exceptions, share the same genetic code, the standard genetic code (SGC). While it remains unclear why this universal code has arisen and been maintained during evolution, it may have been preserved under selection pressure. Theoretical studies comparing the SGC and numerically created hypothetical random genetic codes have suggested that the SGC has been subject to strong selection pressure for being robust against translation errors. However, these prior studies have searched for random genetic codes in only a small subspace of the possible code space due to limitations in computation time. Thus, how the genetic code has evolved, and the characteristics of the genetic code fitness landscape, remain unclear. By applying multicanonical Monte Carlo, an efficient rare-event sampling method, we efficiently sampled random codes from a much broader random ensemble of genetic codes than in previous studies, estimating that only one out of every $10^{20}$ random codes is more robust than the SGC. This estimate is significantly smaller than the previous estimate, one in a million. We also characterized the fitness landscape of the genetic code that has four major fitness peaks, one of which includes the SGC. Furthermore, genetic algorithm analysis revealed that evolution under such a multi-peaked fitness landscape could be strongly biased toward a narrow peak, in an evolutionary path-dependent manner.

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