Soft selective sweeps: Addressing new definitions, evaluating competing models, and interpreting empirical outliers.

Jeffrey D Jensen,Parul Johri,Justin C Fay,Wolfgang Stephan

doi:10.1371/journal.pgen.1010022

Jeffrey D Jensen, Parul Johri + Show 2 more

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https://doi.org/10.1371/journal.pgen.1010022

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Abstract

The ability to accurately identify and quantify genetic signatures associated with soft selective sweeps based on patterns of nucleotide variation has remained controversial. We here provide counter viewpoints to recent publications in PLOS Genetics that have argued not only for the statistical identifiability of soft selective sweeps, but also for their pervasive evolutionary role in both Drosophila and HIV populations. We present evidence that these claims owe to a lack of consideration of competing evolutionary models, unjustified interpretations of empirical outliers, as well as to new definitions of the processes themselves. Our results highlight the dangers of fitting evolutionary models based on hypothesized and episodic processes without properly first considering common processes and, more generally, of the tendency in certain research areas to view pervasive positive selection as a foregone conclusion.

Highlights

A hard sweep refers to the subset of scenarios in which the beneficial variant exists on a single haplotype at the target of selection upon the conclusion of the sweep and is generally associated with a model in which the selective phase was entered while the beneficial allele was rare in the population
A soft sweep generally refers to a subset of scenarios in which multiple haplotypes carry the beneficial variant upon the conclusion of the sweep and is often associated with models in which the beneficial allele was either introduced into the population rapidly via independent mutational events or in which the variant was segregating as a common mutation on multiple distinct haplotypes at the onset of selection
There exist compelling reasons to begin with a null baseline model consisting of evolutionary processes that are certain to be in constant operation, as opposed to models centered upon hypothesized and episodic processes such as selective sweeps [43–45]

Summary

Introduction

We write to provide counter viewpoints to those expressed by Garud, Messer, & Petrov 2021 [2] and Feder, Pennings, & Petrov 2021 [3], both of which were written in response to the work of Harris, Sackman, & Jensen 2018 [4]. The third and much more general point fundamentally underlying this debate is well emphasized in the response of Garud, Messer, & Petrov 2021 [2], who defended their earlier claims of abundant soft sweeps in D. melanogaster [32] and relates to the interpretation of multiple competing models and empirical distributions From their Abstract, “Recently, Harris et al 2018 criticized this work, suggesting that all the candidate loci detected by our haplotype statistics, including the positive controls, are unlikely to be sweeps at all and that instead these haplotype patterns can be more explained by complex neutral demographic models. The observation that opposing models may be fit to a given data observation is a statement of identifiability—that is, additional data and/or analysis is needed to better distinguish the possibilities

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