In a wide variety of organisms, synonymous codons are used with different frequencies, a phenomenon known as codon bias. Population genetic studies have shown that synonymous sites are under weak selection and that codon bias is maintained by a balance between selection, mutation, and genetic drift. It appears that the major cause for selection on codon bias is that certain preferred codons are translated more accurately and/or efficiently. However, additional and sometimes maybe even contradictory selective forces appear to affect codon usage as well. In this review, we discuss the current understanding of the ways in which natural selection participates in the creation and maintenance of codon bias. We also raise several open questions: (i) Is natural selection weak independently of the level of codon bias? It is possible that selection for preferred codons is weak only when codon bias approaches equilibrium and may be quite strong on genes with codon bias levels that are much lower and/or above equilibrium. (ii) What determines the identity of the major codons? (iii) How do shifts in codon bias occur? (iv) What is the exact nature of selection on codon bias? We discuss these questions in depth and offer some ideas on how they can be addressed using a combination of computational and experimental analyses.

中文翻译：

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选择密码子偏倚。

在各种各样的生物中，同义密码子使用的频率不同，这种现象称为密码子偏倚。群体遗传学研究表明，同义位点处于弱选择之下，并且通过选择，突变和遗传漂移之间的平衡来维持密码子偏倚。似乎选择密码子偏倚的主要原因是某些优选的密码子被更准确和/或更有效地翻译。但是，附加的，有时甚至是矛盾的选择力似乎也会影响密码子的使用。在这篇综述中，我们讨论了对自然选择参与创建和维持密码子偏倚的方式的当前理解。我们还提出了几个未解决的问题：（i）自然选择是否弱于密码子偏倚水平？仅当密码子偏倚接近平衡时，对首选密码子的选择才可能是微弱的，而对于密码子偏倚水平远远低于和/或高于平衡的基因，可能会非常强。（ii）是什么决定主要密码子的身份？（iii）密码子偏倚如何发生？（iv）选择密码子偏倚的确切性质是什么？我们将深入讨论这些问题，并提供一些有关如何结合使用计算分析和实验分析来解决这些问题的想法。（ii）是什么决定主要密码子的身份？（iii）密码子偏倚如何发生？（iv）选择密码子偏倚的确切性质是什么？我们将深入讨论这些问题，并提供一些有关如何结合使用计算分析和实验分析来解决这些问题的想法。（ii）是什么决定主要密码子的身份？（iii）密码子偏倚如何发生？（iv）选择密码子偏倚的确切性质是什么？我们将深入讨论这些问题，并提供一些有关如何结合使用计算分析和实验分析来解决这些问题的想法。