'Dissertation Research: Genetic Variation in Induction Kinetics and Antibacterial Strength of Drosophila Immunity Genes'

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0073598Clark & LazzaroInsects face a diverse array of pathogens, which they combat with a generalized immune response. There is extensive genetic variation in immune responsiveness among Drosophila lines derived from a wild population, with differences between lines in mortality rate following infection and in internal pathogen load sustained during infection. A substantial component of the Drosophila immune response is provided by antibacterial peptides which are synthesized in response to septic injury. Preliminary results also show significant variation among Drosophila lines in the transcriptional inducibility of one antibacterial peptide. While previous and ongoing surveys of DNA sequence variation have uncovered coding variants in Drosophila antibacterial peptides, variation in the speed and strength of transcriptional induction of these genes following an infection may also be important. This study will thoroughly quantify the amount of phenotypic variation in immune efficacy segregating in a natural population of Drosophila melanogaster. Mortality rate following infection, suppression of internal pathogen growth, and the transcriptional inducibility of six antibacterial genes will be examined in 150 2nd-chromosome replacement lines of D. melanogaster. Correlations between induction kinetics and immunity will be explored. Several immune system genes will be completely sequenced in a subset of these lines, and molecular markers will be scored in all lines. Statistical associations between nucleotide polymorphisms in antibacterial gene promoters, the transcriptional intensity of those genes, and whole organism phenotypes will be tested. This work will provide a first look at the structure of natural genetic variation in innate immune responsiveness, and will address fundamental question of how natural selection drives the evolution of transcriptional control and innate immunity.