Detection of hard and soft selective sweeps from<i>Drosophila melanogaster</i>population genomic data

Garud, Nandita R.; Messer, Philipp W.; Petrov, Dmitri A.

doi:10.1101/2020.06.20.163261

Cited by 3 publications

(1 citation statement)

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“…If 1 or more additional beneficial mutations enter the population before the first one fixes, the result is a soft sweep. It is therefore possible under certain circumstances to determine θ by looking for characteristic signatures of hard and soft sweeps [ 7 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

The clarifying role of time series data in the population genetics of HIV

2021

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HIV can evolve remarkably quickly in response to antiretroviral therapies and the immune system. This evolution stymies treatment effectiveness and prevents the development of an HIV vaccine. Consequently, there has been a great interest in using population genetics to disentangle the forces that govern the HIV adaptive landscape (selection, drift, mutation, and recombination). Traditional population genetics approaches look at the current state of genetic variation and infer the processes that can generate it. However, because HIV evolves rapidly, we can also sample populations repeatedly over time and watch evolution in action. In this paper, we demonstrate how time series data can bound evolutionary parameters in a way that complements and informs traditional population genetic approaches. Specifically, we focus on our recent paper (Feder et al., 2016, eLife), in which we show that, as improved HIV drugs have led to fewer patients failing therapy due to resistance evolution, less genetic diversity has been maintained following the fixation of drug resistance mutations. Because soft sweeps of multiple drug resistance mutations spreading simultaneously have been previously documented in response to the less effective HIV therapies used early in the epidemic, we interpret the maintenance of post-sweep diversity in response to poor therapies as further evidence of soft sweeps and therefore a high population mutation rate (θ) in these intra-patient HIV populations. Because improved drugs resulted in rarer resistance evolution accompanied by lower post-sweep diversity, we suggest that both observations can be explained by decreased population mutation rates and a resultant transition to hard selective sweeps. A recent paper (Harris et al., 2018, PLOS Genetics) proposed an alternative interpretation: Diversity maintenance following drug resistance evolution in response to poor therapies may have been driven by recombination during slow, hard selective sweeps of single mutations. Then, if better drugs have led to faster hard selective sweeps of resistance, recombination will have less time to rescue diversity during the sweep, recapitulating the decrease in post-sweep diversity as drugs have improved. In this paper, we use time series data to show that drug resistance evolution during ineffective treatment is very fast, providing new evidence that soft sweeps drove early HIV treatment failure.

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Section: Introductionmentioning

confidence: 99%

The clarifying role of time series data in the population genetics of HIV

2021

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The population genomics of adaptive loss of function

et al. 2021

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Discoveries of adaptive gene knockouts and widespread losses of complete genes have in recent years led to a major rethink of the early view that loss-of-function alleles are almost always deleterious. Today, surveys of population genomic diversity are revealing extensive loss-of-function and gene content variation, yet the adaptive significance of much of this variation remains unknown. Here we examine the evolutionary dynamics of adaptive loss of function through the lens of population genomics and consider the challenges and opportunities of studying adaptive loss-of-function alleles using population genetics models. We discuss how the theoretically expected existence of allelic heterogeneity, defined as multiple functionally analogous mutations at the same locus, has proven consistent with empirical evidence and why this impedes both the detection of selection and causal relationships with phenotypes. We then review technical progress towards new functionally explicit population genomic tools and genotype-phenotype methods to overcome these limitations. More broadly, we discuss how the challenges of studying adaptive loss of function highlight the value of classifying genomic variation in a way consistent with the functional concept of an allele from classical population genetics.

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Genome resequencing reveals rapid, repeated evolution in the Colorado potato beetle,Leptinotarsa decemlineata

Pélissié

Chen

et al. 2021

Preprint

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Background: Insecticide resistance and rapid pest evolution threatens food security and the development of sustainable agricultural practices. An improved understanding of the evolutionary mechanisms that allow pests to rapidly adapt to novel control tactics will help prevent economically damaging outbreaks. The Colorado potato beetle (CPB), Leptinotarsa decemlineata, is a global super-pest that rapidly evolves resistance to insecticides. Using whole genome resequencing and transcriptomic data focused on its ancestral and pest range in North America, we assess evidence for three, non-mutually exclusive models of rapid evolution: pervasive selection on novel mutations, rapid regulatory evolution, and repeated selection on standing genetic variation. Results: Population genomic analysis demonstrates that CPB is geographically structured, even among recently established pest populations. Pest populations exhibit only modest reductions in nucleotide diversity, relative to non-pest ancestral populations, and show evidence of recent demographic expansion. Genome scans of selection provide clear signatures of repeated adaptation across different CPB populations, with especially strong evidence that insecticide resistance involves selection of different genes in different populations. Similarly, analyses of gene expression show that constitutive upregulation of candidate insecticide resistance genes drives distinctive population patterns. Conclusion: CPB evolves insecticide resistance repeatedly across agricultural regions, and oftentimes at the same loci, supporting a prominent role of polygenic evolution from standing genetic variation. Despite expectations, we do not find support for strong selection on novel mutations, or rapid evolution from selection on regulatory genes. An important future goal will be to understand how polygenic resistance phenotypes spread among local pest populations, in order to refine integrated pest management practices to maintain the efficacy and sustainability of novel control techniques.

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Detection of hard and soft selective sweeps fromDrosophila melanogasterpopulation genomic data

Cited by 3 publications

References 71 publications

The clarifying role of time series data in the population genetics of HIV

The clarifying role of time series data in the population genetics of HIV

The population genomics of adaptive loss of function

Genome resequencing reveals rapid, repeated evolution in the Colorado potato beetle,Leptinotarsa decemlineata

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