Allelic gene conversion softens selective sweeps

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: classic 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 haplotypes bearing 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 allele 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 in large populations usually involve multiple haplotypes, especially when selection is not extremely strong. Thus, even when the mutation rate is low or there is no standing variation, signatures of hard sweeps are expected to be the exception rather than the rule in large populations. We also summarize patterns of haplotypic diversity following pseudo-soft sweeps, and show that they often resemble those produced by true soft sweeps. It follows that the presence of signatures of soft sweeps does not necessarily mean that adaptation has been especially rapid or is not mutation limited.