Segregation Distorter (SD) is a well-studied selfish gene complex in D. melanogaster. In SD/SD+ heterozygous males, the SD chromosome is transmitted to 95% of the progeny by killing spermatids that have sensitive alleles of its target locus, Responder (Rsp)- a large satellite repeat near the centromere of chromosome 2. Despite knowing the molecular identity of both the distorter and the target, the mechanism behind distortion is unknown.
We use genomic, genetic, molecular and cytological approaches to study the mechanism behind segregation distortion and the effects of selfish genes on genome evolution and the genetic control of spermatogenesis. Our focus is primarily on the Responder satellite and the possibility that small Rsp RNAs are affected by SD in the testis.
Modifiers of SD exist across the genome. Three enhancers of segregation distortion located on the 2nd chromosome ( E(SD), M(SD), and St(SD) ) are frequently held in linkage disequilibrium with the driver through inversions. Suppressors of segregation distortion on the 3rd ( Su(SD)3 ) and X chromosomes ( Su(SD)X ) segregate at high frequencies in natural populations. The molecular identities of these modifiers are currently unknown but discovering their identities promises to provide important insight into the mechanism behind segregation distortion. We are using genetic and association mapping methods to map the modifiers of SD.
Satellite DNAs make up a large fraction of eukaryotic genomes and have have important functions in chromosome pairing and segregation. The rapid evolution of satellite DNAs is a major force contributing to genome evolution across taxa and is implicated in genetic incompatibilities between species.
We use genomic, molecular and cytological techniques to study the forces driving the rapid divergence at satellite repeats in Drosophila populations and across Drosophila species. By developing methods to quantify satellite repeats using next generation sequencing and other molecular approaches, we have the ability to study the dynamics of satellite DNA evolution on a fine time scale.
The misregulation of satellite DNA is linked to genome instability, some cancers, and hybrid dysgenesis. We currently know little about the regulation of satellite DNA and the origin of satellite-derived RNAs. We use molecular, genomic and cytological approaches to study the expression of satellite DNA across Drosophila species.
Drosophila population genetics
The efficacy of both positive and negative selection is reduced in regions of the genome with low recombination. Some evidence suggests that these regions of the genome have adaptive histories despite the reduced efficacy of selection. We use population genetic approaches to study the evolutionary history of the most enigmatic regions of fly genomes:
Y chromosomes: Despite being gene-poor and non-recombining, the Y chromosome of D. melanogaster harbors functionally important variation. In collaboration with Dr. Andy Clark at Cornell University, we studied patterns of diversity of Y chromosomes in D. melanogaster populations from across the globe and found signs of recent adaptation in Africa.
Dot chromosomes: A Y-Autosome translocation even has moved the ancestral Drosophila Y chromosome to the small, non-recombining and heterochromatic dot chromosome of Drosophila pseudoobscura and D. persimilis. In collaboration with Dr. Andy Clark, we studied the evolutionary history of this remarkable genome rearrangement.
Driving chromosomes: SD chromosomes acquire recombination-suppressing inversions to prevent suicidal combinations of driver and target and to keep the driver and enhancers in linkage disequilibrium. While offering short-term benefits, this suppressed recombination comes at a cost: SD chromosomes accumulate deleterious mutations owing to their chromosomal inversions. In collaboration with Daven Presgraves, at the University of Rochester, we are using population genomics to study the effects of suppressed recombination and adaptation across entire SD chromosomes from across the world.