Genetic & Molecular Analysis Of Hybrid Incompatibility In Drosophila.

Abstract

Over evolutionary time genomes diverge by acquiring new mutations, some of which isolate species by erecting reproductive barriers. The study of such genes sheds light on how fundamental developmental processes diverge and result in new species. Hybrid incompatibility (HI) genes contribute to speciation by causing the sterility and inviability of interspecific offspring. The Hmr (Hybrid male rescue) and Lhr (Lethal hybrid rescue) genes are a major cause of hybrid lethality between Drosophila melanogaster and its sibling species D. simulans. Hybrid sons from this cross are normally inviable; however by mutating either the D. melanogaster ortholog of Hmr or the D. simulans ortholog of Lhr, viable adult hybrid sons are recovered. Like other HI genes, both Lhr and Hmr are rapidly evolving under selection. In the first study, I asked whether the evolutionary history of selection for Hmr is confined to the hybridizing lineages. I conducted a population genetic survey of Hmr alleles from two sister species D. yakuba and D. santomea, whose common ancestor diverged from the common ancestor of D. melanogaster and D. simulans approximately 10 Myrs ago. I found that Hmr has diverged recurrently under positive selection in multiple independent speciation events, suggesting that Hmr is likely to be functionally diverging in multiple species. In the second study, I examined the molecular nature of functional divergence for the HI gene, Lhr. Strikingly, I found that despite rapid evolution of the Lhr coding sequence, hybrid lethal activity is not a derived function specific to one lineage, but instead a conserved function shared by both Lhr orthologs. Examination of the heterochromatic localization patterns of Lhr orthologs also failed to reveal any evidence of functional divergence. Instead I discovered that regulatory divergence underlies the asymmetric hybrid lethal activities of Lhr orthologs. In the last study, I identified Lhr2 , a D. simulans Lhr allele with a highly unusual coding sequence, as a hybrid rescue mutation. I used it to identify a conserved region in the C-terminus of the LHR protein that is critical for hybrid incompatibility. Using the Lhr2 allele I was able to assay the effect of an indel polymorphism that was segregating in the common ancestor of D. melanogaster and D. simulans on hybrid incompatibility. Notably, I found that this indel polymorphism contributes significantly to the functional divergence of Lhr.