Estimating the Rate of Adaptive Molecular Evolution When the Evolutionary Divergence Between Species is Small
Estimating the Rate of Adaptive Molecular Evolution When the Evolutionary Divergence Between Species is Small
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DOI：
10.1007/s00239-012-9488-1
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发表时间：
2012-02-01
影响因子：
3.9
通讯作者：
Eyre-Walker, Adam
中科院分区：
文献类型：
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作者：
Keightley, Peter D.;Eyre-Walker, Adam
我们调查的程度，通过扩展麦克唐纳-Kreitman测试获得的自适应分子进化的速率的估计是有偏见的，如果物种，进行分析，分歧最近。我们发现，估计可能是有偏见的，如果物种之间的核苷酸分歧是低相对于物种内的变化，和偏差的大小取决于适应性进化的速度和分布的健身效果的新突变。偏倚似乎是由于三个因素：（1）多态性对分歧的错误归因;（2）祖先多态性对分歧的贡献;（3）中性和有利突变的固定率不同。如果几乎没有适应性分子进化，那么轻微的有害突变会夸大适应性进化速率的估计，因为这些突变对多态性的贡献比中性突变对核苷酸分歧的贡献更大。然而，如果有大量的适应性进化，多态性有助于明显的分歧可能向下偏估计。我们提出了一个简单的方法来纠正轻微有害和中性突变的多态性和分歧的不同贡献，并将其应用到几个物种的数据集。我们发现，从密切相关的物种的适应性分子进化的速度估计可能被低估了10%或更多。然而，在多态性的分歧的贡献被删除后，适应性进化的速度可能仍然被高估的祖先多态性和固定的影响时间的结果。如果分支长度小于10 N（e）代，则该偏差可能是显著的。
We investigate the extent by which the estimates of the rate of adaptive molecular evolution obtained by extending the McDonald-Kreitman test are biased if the species, subjected to analysis, diverged recently. We show that estimates can be biased if the nucleotide divergence between the species is low relative to within species variation, and that the magnitude of the bias depends on the rate of adaptive evolution and the distribution of fitness effects of new mutations. Bias appears to be because of three factors: (1) misattribution of polymorphism to divergence; (2) the contribution of ancestral polymorphism to divergence; and (3) different rates of fixation of neutral and advantageous mutations. If there is little adaptive molecular evolution, then slightly deleterious mutations inflate estimates of the rate of adaptive evolution, because these contribute proportionately more to polymorphism than to nucleotide divergence than neutral mutations. However, if there is substantial adaptive evolution, polymorphism contributing to apparent divergence may downwardly bias estimates. We propose a simple method for correcting the different contributions of slightly deleterious and neutral mutations to polymorphism and divergence, and apply it to datasets from several species. We find that estimates of the rate of adaptive molecular evolution from closely related species may be underestimates by similar to 10% or more. However, after the contribution of polymorphism to divergence is removed, the rate of adaptive evolution may still be overestimated as a consequence of ancestral polymorphism and time for fixation effects. This bias may be substantial if branch lengths are less than 10N (e) generations.