Evolutionary Genomics of Drosophila
Transposable elements (TEs) are highly mutagenic: TE insertions are responsible for more than 100 Mendelian diseases in humans and almost half of all spontaneous mutant phenotypes in Drosophila. To reduce the mutational burden of TEs, host genomes use a variety of mechanisms to suppress their activity, including piwi-interacting small RNAs (piRNAs). However, the ubiquity of active TEs suggests that host silencing mechanisms are not completely effective, possibly because TEs and their host genome are engaged in an evolutionary arms race with TEs selfishly evolving to avoid host silencing and the host genome constantly reestablishing TE suppression. On the host side, many TE silencing components have been shown to be evolving rapidly under positive selection, in agreement with ongoing host-TE conflict. However, there are surprisingly few examples of TE strategies to block or evade host silencing. Our lab is working to identify and characterize such mechanisms which will increase our understanding of how TEs modulate host phenotypes and disease states.
Evolution of the 3D genome
The genomes of most metazoan species are organized into domains of interacting chromatin known as TADs, whose purpose is believed to be related to regulating gene expression by preventing improper enhancer/promoter contacts. We are using Hi-C chromosome conformation capture to study the evolutionary conservation and divergence of TADs and TAD boundaries across Drosophila. Contrary to early studies, we find that overall, the 3D genome evolves relatively rapidly. Furthermore, we do not find significant evidence for a relationship between TAD reorganization and differential gene expression between species. Importantly, we find that the rate of TAD evolution depends on chromatin state, with TADs enriched for developmentally regulated chromatin being the most conserved. Our results raise the possibility that there are different subtypes of TADs that evolve under different selective regimes. Reorganization of TADs enriched for housekeeping genes is likely to be tolerated more than TADs enriched for developmental genes, potentially due to the increased number of long-distance regulatory elements associated with genes involved in development.