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

• Published in: PLoS pathogens 2017-03, Vol.13 (3), p.e1006260
• Main Authors: Wang, Jonathan B, Lu, Hsiao-Ling, St Leger, Raymond J
• Format: Article
• Language: English
• Subjects: Age; Agronomy; Animals; Antiinfectives and antibacterials; Axon guidance; Bacteria; Bacterial infections; Biological control; Biological effects; Biological evolution; Biology; Biology and Life Sciences; Borers; Cadmium; Circadian rhythms; Coagulation; Coffee; Colleges & universities; Competitiveness; Construction; Correlation; Data acquisition; Data collection; Deoxyribonucleic acid; Disease resistance; Disease susceptibility; DNA; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - microbiology; Ecology; Ecosystems; Effectors; Enzymes; Extinct species; Fecundity; Food; Food security; Fruits; Fungal infections; Fungi; Fungicides; Genetic aspects; Genetic polymorphisms; Genetic variation; Genetics; Genome-Wide Association Study; Glucose; Hemolymph; Homology; Immune response; Immune system; Infections; Insects; Insertional mutagenesis; Longevity; Malaria; Mating; Medicine and Health Sciences; Metabolism; Metarhizium; Microbial drug resistance; Mutagenesis, Insertional; Mutagenesis, Site-Directed; Oxidative stress; Parasites; Pathogenicity; Pathogens; Pest control; Pests; Physiology; Proteins; Pseudomonas aeruginosa; Regulators; Research and Analysis Methods; Science; Stability; Starvation; Survival; Tropical diseases; Viruses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006260

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.