On the unfounded enthusiasm for soft selective sweeps II: Examining recent evidence from humans, flies, and viruses

Rebecca B Harris, Andrew Sackman and Jeffrey D Jensen

PLOS Genetics, 2018, vol. 14, issue 12, 1-21

Abstract: Since the initial description of the genomic patterns expected under models of positive selection acting on standing genetic variation and on multiple beneficial mutations—so-called soft selective sweeps—researchers have sought to identify these patterns in natural population data. Indeed, over the past two years, large-scale data analyses have argued that soft sweeps are pervasive across organisms of very different effective population size and mutation rate—humans, Drosophila, and HIV. Yet, others have evaluated the relevance of these models to natural populations, as well as the identifiability of the models relative to other known population-level processes, arguing that soft sweeps are likely to be rare. Here, we look to reconcile these opposing results by carefully evaluating three recent studies and their underlying methodologies. Using population genetic theory, as well as extensive simulation, we find that all three examples are prone to extremely high false-positive rates, incorrectly identifying soft sweeps under both hard sweep and neutral models. Furthermore, we demonstrate that well-fit demographic histories combined with rare hard sweeps serve as the more parsimonious explanation. These findings represent a necessary response to the growing tendency of invoking parameter-heavy, assumption-laden models of pervasive positive selection, and neglecting best practices regarding the construction of proper demographic null models.Author summary: A long-standing debate in evolutionary biology revolves around the role of selective vs. stochastic processes in driving molecular evolution and shaping genetic variation. With the advent of genomics, genome-wide polymorphism data have been utilized to characterize these processes, with a major interest in describing the fraction of genomic variation shaped by positive selection. These genomic scans were initially focused around a hard sweep model, in which selection acts upon rare, newly arising beneficial mutations. Recent years have seen the description of sweeps occurring from both standing and rapidly recurring beneficial mutations, collectively known as soft sweeps. However, common to both hard and soft sweeps is the difficulty in distinguishing these effects from neutral demographic patterns, and disentangling these processes has remained an important field of study within population genetics. Despite this, there is a recent and troubling tendency to neglect these demographic considerations, and to naively fit sweep models to genomic data. Recent realizations of such efforts have resulted in the claim that soft sweeps play a dominant role in shaping genomic variation and in driving adaptation across diverse branches of the tree of life. Here, we reanalyze these findings and demonstrate that a more careful consideration of neutral processes results in highly differing conclusions.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1007859

DOI: 10.1371/journal.pgen.1007859

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