Genome-Wide Association Studies Reveal a Simple Genetic Basis of Resistance to Naturally Coevolving Viruses in Drosophila melanogaster

Magwire, Michael M.; Fabian, Daniel K.; Schweyen, Hannah; Cao, Chuan; Longdon, Ben; Bayer, Florian; Jiggins, Francis M.

doi:10.1371/journal.pgen.1003057

Cited by 157 publications

(258 citation statements)

References 62 publications

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“…However, the genetic architecture of susceptibility to infectious diseases may be different (Hill 2012; Magwire et al . 2012). Major‐effect polymorphisms that decrease susceptibility to infection have been identified in many organisms by both GWAS and classical QTL and linkage mapping (Bangham et al .…”

Section: Introductionmentioning

confidence: 99%

“…This suggests that natural selection may increase the frequency of major‐effect alleles in populations, causing the genetic architecture of susceptibility to infectious diseases to be simpler than is the case for noncommunicable diseases (Hill 2012; Magwire et al . 2012). …”

Section: Introductionmentioning

confidence: 99%

“…2011; #37, Magwire et al . 2012; #36). For DCV, we identified a single major‐effect gene called Pastrel that explains 47% of the genetic variance in resistance (Magwire et al .…”

Section: Introductionmentioning

confidence: 99%

“…For DCV, we identified a single major‐effect gene called Pastrel that explains 47% of the genetic variance in resistance (Magwire et al . 2012). Although these association studies were very successful in explaining a large proportion of genetic variation compared to most studies on the genetic basis of complex traits, there is still a large proportion of genetic variation not explained, and the causes of this missing heritability are unknown.…”

Section: Introductionmentioning

confidence: 99%

“…This previous work used a panel of fly lines (the DGRP lines) from a population in North America that had been inbred and had their genomes resequenced (Magwire et al . 2012). We were limited to c .…”

Section: Introductionmentioning

confidence: 99%

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The genetic architecture of resistance to virus infection in Drosophila

et al. 2016

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Variation in susceptibility to infection has a substantial genetic component in natural populations, and it has been argued that selection by pathogens may result in it having a simpler genetic architecture than many other quantitative traits. This is important as models of host–pathogen co‐evolution typically assume resistance is controlled by a small number of genes. Using the Drosophila melanogaster multiparent advanced intercross, we investigated the genetic architecture of resistance to two naturally occurring viruses, the sigma virus and DCV (Drosophila C virus). We found extensive genetic variation in resistance to both viruses. For DCV resistance, this variation is largely caused by two major‐effect loci. Sigma virus resistance involves more genes – we mapped five loci, and together these explained less than half the genetic variance. Nonetheless, several of these had a large effect on resistance. Models of co‐evolution typically assume strong epistatic interactions between polymorphisms controlling resistance, but we were only able to detect one locus that altered the effect of the main effect loci we had mapped. Most of the loci we mapped were probably at an intermediate frequency in natural populations. Overall, our results are consistent with major‐effect genes commonly affecting susceptibility to infectious diseases, with DCV resistance being a near‐Mendelian trait.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…2011; #37, Magwire et al . 2012; #36). For DCV, we identified a single major‐effect gene called Pastrel that explains 47% of the genetic variance in resistance (Magwire et al .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The genetic architecture of resistance to virus infection in Drosophila

et al. 2016

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Identifying coevolving loci using interspecific genetic correlations

Nuismer

Jenkins

Dybdahl

2017

Ecology and Evolution

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Evaluating the importance of coevolution for a wide range of evolutionary questions, such as the role parasites play in the evolution of sexual reproduction, requires that we understand the genetic basis of coevolutionary interactions. Despite its importance, little progress has been made identifying the genetic basis of coevolution, largely because we lack tools designed specifically for this purpose. Instead, coevolutionary studies are often forced to re‐purpose single species techniques. Here, we propose a novel approach for identifying the genes mediating locally adapted coevolutionary interactions that relies on spatial correlations between genetic marker frequencies in the interacting species. Using individual‐based multi‐locus simulations, we quantify the performance of our approach across a range of coevolutionary genetic models. Our results show that when one species is strongly locally adapted to the other and a sufficient number of populations can be sampled, our approach accurately identifies functionally coupled host and parasite genes. Although not a panacea, the approach we outline here could help to focus the search for coevolving genes in a wide variety of well‐studied systems for which substantial local adaptation has been demonstrated.

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Between virus correlations in the outcome of infection across host species: Evidence of virus by host species interactions

2021

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Virus host shifts are a major source of outbreaks and emerging infectious diseases, and predicting the outcome of novel host and virus interactions remains a key challenge for virus research. The evolutionary relationships between host species can explain variation in transmission rates, virulence, and virus community composition between hosts, but it is unclear if correlations exist between related viruses in infection traits across novel hosts. Here, we measure correlations in viral load of four Cripavirus isolates across experimental infections of 45 Drosophilidae host species. We find positive correlations between every pair of viruses tested, suggesting that some host clades show broad susceptibility and could act as reservoirs and donors for certain types of viruses. Additionally, we find evidence of virus by host species interactions, highlighting the importance of both host and virus traits in determining the outcome of virus host shifts. Of the four viruses tested here, those that were more closely related tended to be more strongly correlated, providing tentative evidence that virus evolutionary relatedness may be a useful proxy for determining the likelihood of novel virus emergence, which warrants further research.

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Genome-Wide Association Studies Reveal a Simple Genetic Basis of Resistance to Naturally Coevolving Viruses in Drosophila melanogaster

Cited by 157 publications

References 62 publications

The genetic architecture of resistance to virus infection in Drosophila

The genetic architecture of resistance to virus infection in Drosophila

Identifying coevolving loci using interspecific genetic correlations

Between virus correlations in the outcome of infection across host species: Evidence of virus by host species interactions

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