A population and quantitative genetic analysis of the Drosophila melanogaster antibacterial immune response
Open Access
- Author:
- Lazzaro, Brian Paul
- Graduate Program:
- Biology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 27, 2002
- Committee Members:
- Stephen Wade Schaeffer, Committee Chair/Co-Chair
Thomas Whittam, Committee Member
Andrew Clark, Committee Chair/Co-Chair
Hiroshi Akashi, Committee Member
Diana Lynn Cox Foster, Committee Member - Keywords:
- Drosophila melanogaster
population genetics
quantitative genetics
innate immunity
antibacterial
SNP
association study
pathogen
bacteria - Abstract:
- Insects respond to microbial infection with a potent generalized immune response that has cellular and humoral components. Recognition of invariant microbial compounds triggers both phagocytosis of the invading microorganism and the synthesis of extracellularly circulated antibiotic peptides. This is an evolutionarily ancient and conserved approach to immunity, and many of the proteins involved have homologs in vertebrate innate immune systems. In this thesis, I consider population-level variability in Drosophila melanogaster antibacterial immune responses from three distinct, but related, perspectives. In the most focused experiments, I survey polymorphism in genes encoding inducible antibacterial peptides in a North American D. melanogaster population sample. I find evidence for recurrent gene conversion between tandemly repeated Attacin genes and an apparent excess of non-conservative amino acid polymorphism in processed peptide domains. Patterns of nucleotide polymorphism suggest that natural selection and demographic history have shaped the evolution of peptide genes as a functional class. In a more inclusive approach, I measure phenotypic variation in the ability suppress pathogenic infection among flies sampled from the same North American population. I then employ candidate gene based association tests to identify naturally occurring alleles of 13 genes that contribute to phenotypic variability in immunocompetence. The strongest associations are found in pathogen recognition genes, with many associations being sex-limited or affected by circadian day. In the most ecological study, I examine the frequency of bacterial infection in the sampled D. melanogaster population in both September and October of 1998 and 2001, culturing and identifying isolated pathogens. I find that ascertained infection declines between early and late fall, and identify 18 bacterial species in 15 genera as potential Drosophila pathogens. I show that several of the isolates can induce Drosophila mortality and a few persist in the hemolymph for days after artificial infection. As a whole, this thesis presents a comprehensive look at natural variation in the antibacterial immune responses of D. melanogaster, addressing several fundamental questions about variability in such systems and raising topics for further research.