The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel.

Individuals vary extensively in the way they respond to disease but the genetic basis of this variation is not fully understood. We found substantial individual variation in resistance and tolerance to the fungal pathogen Metarhizium anisopliae Ma549 using the Drosophila melanogaster Genetic Referen...

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Main Authors: Jonathan B Wang, Hsiao-Ling Lu, Raymond J St Leger
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-03-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC5352145?pdf=render
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spelling doaj-dc7cb9a607344d499a05bf7313776c092020-11-24T22:10:37ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-03-01133e100626010.1371/journal.ppat.1006260The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel.Jonathan B WangHsiao-Ling LuRaymond J St LegerIndividuals vary extensively in the way they respond to disease but the genetic basis of this variation is not fully understood. We found substantial individual variation in resistance and tolerance to the fungal pathogen Metarhizium anisopliae Ma549 using the Drosophila melanogaster Genetic Reference Panel (DGRP). In addition, we found that host defense to Ma549 was correlated with defense to the bacterium Pseudomonas aeruginosa Pa14, and several previously published DGRP phenotypes including oxidative stress sensitivity, starvation stress resistance, hemolymph glucose levels, and sleep indices. We identified polymorphisms associated with differences between lines in both their mean survival times and microenvironmental plasticity, suggesting that lines differ in their ability to adapt to variable pathogen exposures. The majority of polymorphisms increasing resistance to Ma549 were sex biased, located in non-coding regions, had moderately large effect and were rare, suggesting that there is a general cost to defense. Nevertheless, host defense was not negatively correlated with overall longevity and fecundity. In contrast to Ma549, minor alleles were concentrated in the most Pa14-susceptible as well as the most Pa14-resistant lines. A pathway based analysis revealed a network of Pa14 and Ma549-resistance genes that are functionally connected through processes that encompass phagocytosis and engulfment, cell mobility, intermediary metabolism, protein phosphorylation, axon guidance, response to DNA damage, and drug metabolism. Functional testing with insertional mutagenesis lines indicates that 12/13 candidate genes tested influence susceptibility to Ma549. Many candidate genes have homologs identified in studies of human disease, suggesting that genes affecting variation in susceptibility are conserved across species.http://europepmc.org/articles/PMC5352145?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Jonathan B Wang
Hsiao-Ling Lu
Raymond J St Leger
spellingShingle Jonathan B Wang
Hsiao-Ling Lu
Raymond J St Leger
The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel.
PLoS Pathogens
author_facet Jonathan B Wang
Hsiao-Ling Lu
Raymond J St Leger
author_sort Jonathan B Wang
title The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel.
title_short The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel.
title_full The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel.
title_fullStr The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel.
title_full_unstemmed The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel.
title_sort genetic basis for variation in resistance to infection in the drosophila melanogaster genetic reference panel.
publisher Public Library of Science (PLoS)
series PLoS Pathogens
issn 1553-7366
1553-7374
publishDate 2017-03-01
description Individuals vary extensively in the way they respond to disease but the genetic basis of this variation is not fully understood. We found substantial individual variation in resistance and tolerance to the fungal pathogen Metarhizium anisopliae Ma549 using the Drosophila melanogaster Genetic Reference Panel (DGRP). In addition, we found that host defense to Ma549 was correlated with defense to the bacterium Pseudomonas aeruginosa Pa14, and several previously published DGRP phenotypes including oxidative stress sensitivity, starvation stress resistance, hemolymph glucose levels, and sleep indices. We identified polymorphisms associated with differences between lines in both their mean survival times and microenvironmental plasticity, suggesting that lines differ in their ability to adapt to variable pathogen exposures. The majority of polymorphisms increasing resistance to Ma549 were sex biased, located in non-coding regions, had moderately large effect and were rare, suggesting that there is a general cost to defense. Nevertheless, host defense was not negatively correlated with overall longevity and fecundity. In contrast to Ma549, minor alleles were concentrated in the most Pa14-susceptible as well as the most Pa14-resistant lines. A pathway based analysis revealed a network of Pa14 and Ma549-resistance genes that are functionally connected through processes that encompass phagocytosis and engulfment, cell mobility, intermediary metabolism, protein phosphorylation, axon guidance, response to DNA damage, and drug metabolism. Functional testing with insertional mutagenesis lines indicates that 12/13 candidate genes tested influence susceptibility to Ma549. Many candidate genes have homologs identified in studies of human disease, suggesting that genes affecting variation in susceptibility are conserved across species.
url http://europepmc.org/articles/PMC5352145?pdf=render
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