Recent selective sweeps in North American Drosophila melanogaster show signatures of soft sweeps.

Nandita R Garud,Dmitri A Petrov,Philipp W Messer,Erkan O Buzbas,Gregory P Copenhaver

doi:10.1371/journal.pgen.1005004

Nandita R Garud, Dmitri A Petrov + Show 3 more

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https://doi.org/10.1371/journal.pgen.1005004

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Abstract

Adaptation from standing genetic variation or recurrent de novo mutation in large populations should commonly generate soft rather than hard selective sweeps. In contrast to a hard selective sweep, in which a single adaptive haplotype rises to high population frequency, in a soft selective sweep multiple adaptive haplotypes sweep through the population simultaneously, producing distinct patterns of genetic variation in the vicinity of the adaptive site. Current statistical methods were expressly designed to detect hard sweeps and most lack power to detect soft sweeps. This is particularly unfortunate for the study of adaptation in species such as Drosophila melanogaster, where all three confirmed cases of recent adaptation resulted in soft selective sweeps and where there is evidence that the effective population size relevant for recent and strong adaptation is large enough to generate soft sweeps even when adaptation requires mutation at a specific single site at a locus. Here, we develop a statistical test based on a measure of haplotype homozygosity (H12) that is capable of detecting both hard and soft sweeps with similar power. We use H12 to identify multiple genomic regions that have undergone recent and strong adaptation in a large population sample of fully sequenced Drosophila melanogaster strains from the Drosophila Genetic Reference Panel (DGRP). Visual inspection of the top 50 candidates reveals that in all cases multiple haplotypes are present at high frequencies, consistent with signatures of soft sweeps. We further develop a second haplotype homozygosity statistic (H2/H1) that, in combination with H12, is capable of differentiating hard from soft sweeps. Surprisingly, we find that the H12 and H2/H1 values for all top 50 peaks are much more easily generated by soft rather than hard sweeps. We discuss the implications of these results for the study of adaptation in Drosophila and in species with large census population sizes.

Highlights

The ability to identify genomic loci subject to recent positive selection is essential for our efforts to uncover the genetic basis of phenotypic evolution and to understand the overall role of adaptation in molecular evolution
If these mutations were previously rare or absent from the population, adaptation should generate a characteristic signature in the genetic diversity around the adaptive locus, known as a selective sweep
Such selective sweeps can be distinguished into hard selective sweeps, where only a single adaptive mutation rises in frequency, or soft selective sweeps, where multiple adaptive mutations at the same locus sweep through the population simultaneously

Summary

Introduction

The ability to identify genomic loci subject to recent positive selection is essential for our efforts to uncover the genetic basis of phenotypic evolution and to understand the overall role of adaptation in molecular evolution. There is evidence that at least some of these adaptive events were driven by strong positive selection (~1% or larger), depleting levels of genetic variation on scales of tens of thousands of base pairs in length [10,11]. If adaptation in D. melanogaster is common and often driven by strong selection, it should be possible to detect genomic signatures of recent and strong adaptation [12,13,14]. Three cases of recent and strong adaptation in D. melanogaster are well documented and can inform our intuitions about the expected genomic signatures of such adaptive events. Resistance to DDT evolved via a series of adaptive events that included insertion of an Accord transposon in the 5’ regulatory region of the gene Cyp6g1, duplication of the locus, and additional transposable element insertions into the locus [18,19]. Increased resistance to infection by the sigma virus, as well as resistance to certain organophosphates, has been associated with a transposable element insertion in the protein-coding region of the gene CHKov1 [20,21]

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