Weber Claudia C, Nabholz Benoit, Romiguier Jonathan, Ellegren Hans
Genome Biol. 2014;15(12):542. doi: 10.1186/s13059-014-0542-8.
The ratio of the rates of non-synonymous and synonymous substitution (dN/dS) is commonly used to estimate selection in coding sequences. It is often suggested that, all else being equal, dN/dS should be lower in populations with large effective size (Ne) due to increased efficacy of purifying selection. As Ne is difficult to measure directly, life history traits such as body mass, which is typically negatively associated with population size, have commonly been used as proxies in empirical tests of this hypothesis. However, evidence of whether the expected positive correlation between body mass and dN/dS is consistently observed is conflicting.
Employing whole genome sequence data from 48 avian species, we assess the relationship between rates of molecular evolution and life history in birds. We find a negative correlation between dN/dS and body mass, contrary to nearly neutral expectation. This raises the question whether the correlation might be a method artefact. We therefore in turn consider non-stationary base composition, divergence time and saturation as possible explanations, but find no clear patterns. However, in striking contrast to dN/dS, the ratio of radical to conservative amino acid substitutions (Kr/Kc) correlates positively with body mass.
Our results in principle accord with the notion that non-synonymous substitutions causing radical amino acid changes are more efficiently removed by selection in large populations, consistent with nearly neutral theory. These findings have implications for the use of dN/dS and suggest that caution is warranted when drawing conclusions about lineage-specific modes of protein evolution using this metric.
非同义替换率与同义替换率的比值(dN/dS)常用于估计编码序列中的选择作用。通常认为,在其他条件相同的情况下,由于纯化选择效率的提高,有效种群大小(Ne)较大的种群中dN/dS应该更低。由于Ne难以直接测量,在对这一假设的实证检验中,通常使用体重等生活史特征作为替代指标,体重通常与种群大小呈负相关。然而,关于体重与dN/dS之间预期的正相关关系是否始终能被观察到,证据并不一致。
利用48种鸟类的全基因组序列数据,我们评估了鸟类分子进化速率与生活史之间的关系。我们发现dN/dS与体重呈负相关,这与近中性预期相反。这就引发了一个问题,即这种相关性是否可能是一种方法假象。因此,我们转而考虑非平稳碱基组成、分歧时间和饱和度等可能的解释,但没有发现明显的模式。然而,与dN/dS形成鲜明对比的是,激进氨基酸替换与保守氨基酸替换的比值(Kr/Kc)与体重呈正相关。
我们的结果原则上符合这样一种观点,即在大种群中,导致激进氨基酸变化的非同义替换更有效地被选择去除,这与近中性理论一致。这些发现对dN/dS的使用有影响,并表明在使用该指标得出关于谱系特异性蛋白质进化模式的结论时需要谨慎。