Recombination Rate Variation Modulates Gene Sequence Evolution Mainly via GC-Biased Gene Conversion, Not Hill-Robertson Interference, in an Avian System.
Recombination Rate Variation Modulates Gene Sequence Evolution Mainly via GC-Biased Gene Conversion, Not Hill-Robertson Interference, in an Avian System.
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DOI：
10.1093/molbev/msv214
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发表时间：
2016-01
影响因子：
10.7
通讯作者：
Ellegren H
中科院分区：
文献类型：
--
作者：
Bolívar P;Mugal CF;Nater A;Ellegren H
非同义替换率与同义替换率(ω)的比率通常被用来衡量自然选择的强度。然而，ω可能会受到不同选择目标之间的连锁的影响，即希尔-罗伯逊干扰，从而降低了选择的效率。重组调节HRI的程度，但也可能通过GC偏向的基因转换影响ω，这一过程导致G：C(“强”S)优先固定A：T(“弱”W)等位基因。由于HRI和GBGC可能对ω产生相反的影响，因此了解它们的相对影响对于正确推断ω是至关重要的。我们使用了一个模型，分别估计了8,423只苍蝇家系中S对S、S对W、W对S和W对W的替换率。结果发现，W对S的替代率与重组率呈正相关，而S对W的替代率与重组率呈负相关，符合GBGC，但不符合HRI的预测。W-to-S比率对DN和DS的影响最大。然而，由于4倍比0倍退化位点的影响更强，可能是因为这些位点的GC含量远离平衡，ω随着重组率的增加而略有下降，这可能是HRI的结果。我们从理论上证实了这一假设，并证明了在特定条件下，ω可以随着重组率的增加而降低。位点频谱分析表明，W-to-S突变倾向于高频率，S-to-W突变倾向于低频率，这与普遍存在的S基因驱动的固定偏向一致。
The ratio of nonsynonymous to synonymous substitution rates (ω) is often used to measure the strength of natural selection. However, ω may be influenced by linkage among different targets of selection, that is, Hill–Robertson interference (HRI), which reduces the efficacy of selection. Recombination modulates the extent of HRI but may also affect ω by means of GC-biased gene conversion (gBGC), a process leading to a preferential fixation of G:C (“strong,” S) over A:T (“weak,” W) alleles. As HRI and gBGC can have opposing effects on ω, it is essential to understand their relative impact to make proper inferences of ω. We used a model that separately estimated S-to-S, S-to-W, W-to-S, and W-to-W substitution rates in 8,423 avian genes in the Ficedula flycatcher lineage. We found that the W-to-S substitution rate was positively, and the S-to-W rate negatively, correlated with recombination rate, in accordance with gBGC but not predicted by HRI. The W-to-S rate further showed the strongest impact on both dN and dS. However, since the effects were stronger at 4-fold than at 0-fold degenerated sites, likely because the GC content of these sites is farther away from its equilibrium, ω slightly decreases with increasing recombination rate, which could falsely be interpreted as a consequence of HRI. We corroborated this hypothesis analytically and demonstrate that under particular conditions, ω can decrease with increasing recombination rate. Analyses of the site-frequency spectrum showed that W-to-S mutations were skewed toward high, and S-to-W mutations toward low, frequencies, consistent with a prevalent gBGC-driven fixation bias.