Allelic gene conversion softens selective sweeps.
Allelic gene conversion softens selective sweeps.
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等位基因转换软化了选择性扫描。
DOI：
10.1101/2023.12.05.570141
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Schrider,DanielR
中科院分区：
文献类型：
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作者：
Schrider,DanielR
正向选择的突出地位，即有益的突变受到自然选择的青睐，并且频率迅速增加，是一个激烈辩论的主题。正向选择可以导致选择性扫描，即携带适应等位基因的单倍型(S)在群体中“扫描”，从而消除选择目标周围区域的大部分遗传多样性。已经提出了两种选择性扫描模式：经典扫描或“硬扫描”，即单个自适应等位基因拷贝到固定；“软扫描”，即自适应等位基因的多个不同拷贝在扫描后离开后代。软扫描可以是适应等位基因反复突变的结果，也可以是在选择开始之前存在由适应等位基因的多个副本组成的长期遗传变异的结果。重要的是，当种群能够快速适应新的选择压力时，软扫描将很常见，要么是因为高突变率，要么是因为已经存在适应性等位基因。软扫描的流行是特别有争议的，已经注意到，对立地变异或重复突变的选择并不总是产生软扫描。在这里，我们证明相反的是正确的：对单一来源从头开始突变的选择通常会导致与软扫描没有区别的结果。这是由等位基因转换实现的，它通过将适应性等位基因复制到多个遗传背景上来“软化”硬扫描，这一过程我们称为“伪软”扫描。我们在人类、果蝇和拟南芥种群模型中进行了一项模拟研究，考察了基因转换对单个从头变异的扫描的影响。在模拟中，基因转换产生了具有固定的适应等位基因的多种单倍型，这一比例是可观的。事实上，在现实的人口学历史和基因转换率下，即使选择总是作用于单一来源的突变，涉及多个单倍型的扫描在大种群中更有可能比硬扫描更有可能，特别是在选择不是非常强大的情况下。因此，即使在突变率很低或没有固定变异的情况下，在大种群中，硬扫描预计也是例外，而不是规则。这些结果还暗示，软扫描特征的存在并不一定意味着适应特别迅速或不受突变限制。
The prominence of positive selection, in which beneficial mutations are favored by natural selection and rapidly increase in frequency, is a subject of intense debate. Positive selection can result in selective sweeps, in which the haplotype(s) bearing the adaptive allele “sweep” through the population, thereby removing much of the genetic diversity from the region surrounding the target of selection. Two models of selective sweeps have been proposed: classical sweeps, or “hard sweeps”, in which a single copy of the adaptive allele sweeps to fixation, and “soft sweeps”, in which multiple distinct copies of the adaptive allele leave descendants after the sweep. Soft sweeps can be the outcome of recurrent mutation to the adaptive allele, or the presence of standing genetic variation consisting of multiple copies of the adaptive allele prior to the onset of selection. Importantly, soft sweeps will be common when populations can rapidly adapt to novel selective pressures, either because of a high mutation rate or because adaptive alleles are already present. The prevalence of soft sweeps is especially controversial, and it has been noted that selection on standing variation or recurrent mutations may not always produce soft sweeps. Here, we show that the inverse is true: selection on single-origin de novo mutations may often result in an outcome that is indistinguishable from a soft sweep. This is made possible by allelic gene conversion, which “softens” hard sweeps by copying the adaptive allele onto multiple genetic backgrounds, a process we refer to as a “pseudo-soft” sweep. We carried out a simulation study examining the impact of gene conversion on sweeps from a single de novo variant in models of human, Drosophila, and Arabidopsis populations. The fraction of simulations in which gene conversion had produced multiple haplotypes with the adaptive allele upon fixation was appreciable. Indeed, under realistic demographic histories and gene conversion rates, even if selection always acts on a single-origin mutation, sweeps involving multiple haplotypes are more likely than hard sweeps in large populations, especially when selection is not extremely strong. Thus, even when the mutation rate is low or there is no standing variation, hard sweeps are expected to be the exception rather than the rule in large populations. These results also imply that the presence of signatures of soft sweeps does not necessarily mean that adaptation has been especially rapid or is not mutation limited.