Evolutionary Genetics Of The Innate Immune System In Drosophila
The innate immune system has drawn interest with its deep evolutionary conservation and importance in response to infection both in invertebrates, providing the only reaction to invading microbes, and as a generalized first reaction in vertebrates, activating the adaptive response. Drosophila has become a useful model for innate immunity, due to the powerful genetic, genomic and comparative resources available. Drosophila-based research has uncovered many genes involved in these pathways, and studies of the population genetics, interspecific divergence, and gene duplication patterns have revealed evidence for selection acting on immune genes, with distinct evolutionary pressures inferred to act on different functional groups. To investigate variation in immune response within a natural D. melanogaster population, we assayed polymorphism in X-linked immune genes and tested correlations between these variants and immune phenotypes. This revealed associations in numerous immune genes with differences in immunocompetence, and strikingly, many of these genotypes appear to associate with sex differences in immune phenotype. Beyond this segregating variation, we also examined divergence between species. In order to quantify regulatory divergence, we have assayed expression before and after infection in D. melanogaster, D. simulans, and interspecific hybrids. If immune regulation has diverged between species, we expect hybrids to display a disrupted immune response, and we do, in fact, observe immune dysregulation in the hybrids. This was most notable in the downstream pathway components, indicative of propagation of dysregulation throughout the response. To further dissect the dysregulation evident in hybrids, we have quantified immune phenotypes in hybrids bearing mutant melanogaster alleles for genes throughout the innate immune pathways. Resulting animals are forced to employ only the simulans allele at the point of the melanogaster mutation. We find that a mutation in one gene in particular, Dredd, has a detrimental effect in a hybrid background, indicating that Dredd is likely involved in interactions that have evolved to be specific, such that combinations of melanogaster + simulans alleles in Dredd interactions lead to a breakdown in immune activation. Overall, we find strong evidence for immune response divergence between species, but the degree of functionally relevant divergence appears to be greatest among signaling molecules.
dissertation or thesis