The population genetics of dN/dS.
The population genetics of dN/dS.
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DOI：
10.1371/journal.pgen.1000304
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发表时间：
2008-12
期刊：
影响因子：
4.5
通讯作者：
Plotkin JB
中科院分区：
文献类型：
--
作者：
Kryazhimskiy S;Plotkin JB
蛋白质的进化压力通常用非同义和同义位点的代替率之比来量化。DN/ds比率最初是为了应用于远距离分离的序列而开发的，它们之间的差异表示沿着独立谱系固定的替换。然而，dN/ds度量通常应用于从单个群体中采样的序列，它们之间的差异代表分离的多态。在这里，我们研究了从被选择的单个群体中抽取的样本的预期dN/ds比，我们发现在这种情况下，dN/dS对选择系数相对不敏感。此外，正向选择对不同血统的标志性特征dN/ds>；1在种群内被违反。对于总体样本，选择与Dn/DS之间的关系不遵循单调函数，因此可能不可能从Dn/Ds推断选择压力。这些结果对解释群体遗传样本中的dN/ds测量具有重要意义。自达尔文时代以来，生物学家一直致力于识别进化适应的实例。在分子水平上，人们理解，与氨基酸保存位置相比，适应应该在基因组中氨基酸改变位置引起更多的遗传变化。因此，这些位点的替换率比率，表示为dN/ds，通常用于检测正在进行适应的蛋白质。这项测试最初是为应用于相距遥远的遗传序列而开发的，它们之间的差异代表着沿着独立进化谱系的替换。尽管如此，dN/ds统计也经常应用于从单个种群采样的遗传序列，它们之间的差异代表瞬时多态，而不是替换。在这里，我们展示了在这两种情况下，DN/DS统计的行为非常不同。特别是，当应用于来自单个种群的序列时，dN/dS比率对自然选择的强度相对不敏感，并且违反了自适应进化的预期特征dN/dS>；1。这些结果对解释从群体中抽样的遗传变异有一定的意义。特别是，这些结果表明，微生物可能经历了比之前认为的更强的选择性力量。
Evolutionary pressures on proteins are often quantified by the ratio of substitution rates at non-synonymous and synonymous sites. The dN/dS ratio was originally developed for application to distantly diverged sequences, the differences among which represent substitutions that have fixed along independent lineages. Nevertheless, the dN/dS measure is often applied to sequences sampled from a single population, the differences among which represent segregating polymorphisms. Here, we study the expected dN/dS ratio for samples drawn from a single population under selection, and we find that in this context, dN/dS is relatively insensitive to the selection coefficient. Moreover, the hallmark signature of positive selection over divergent lineages, dN/dS>1, is violated within a population. For population samples, the relationship between selection and dN/dS does not follow a monotonic function, and so it may be impossible to infer selection pressures from dN/dS. These results have significant implications for the interpretation of dN/dS measurements among population-genetic samples. Since the time of Darwin, biologists have worked to identify instances of evolutionary adaptation. At the molecular scale, it is understood that adaptation should induce more genetic changes at amino acid altering sites in the genome, compared to amino acid–preserving sites. The ratio of substitution rates at such sites, denoted dN/dS, is therefore commonly used to detect proteins undergoing adaptation. This test was originally developed for application to distantly diverged genetic sequences, the differences among which represent substitutions along independent evolutionary lineages. Nonetheless, the dN/dS statistics are also frequently applied to genetic sequences sampled from a single population, the differences among which represent transient polymorphisms, not substitutions. Here, we show that the behavior of the dN/dS statistic is very different in these two cases. In particular, when applied to sequences from a single population, the dN/dS ratio is relatively insensitive to the strength of natural selection, and the anticipated signature of adaptive evolution, dN/dS>1, is violated. These results have implications for the interpretation of genetic variation sampled from a population. In particular, these results suggest that microbes may experience substantially stronger selective forces than previously thought.
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