Molecular mechanisms of genomic conflicts and hybrid incompatibilities

Utah State Higher Education System--University Of Utah, Salt Lake City UT

Investigators

Abstract

Project summary Understanding the genetic basis and molecular mechanisms of evolutionary conflicts, and how they shape the evolution of genomes, cells, and species is a fundamental goal in biology. In particular, our research program focuses on understanding how molecular arms races involving selfish genetic elements such as segregation distorters and transposable elements can lead to the rapid evolution of essential cellular machinery and contribute to the origins of new species. Using a highly multidisciplinary approach, we aim to understand the genetic and molecular bases of conflict and hybrid incompatibilities in Drosophila. This proposal briefly describes three research directions pursued in my laboratory. First, we aim to understand the molecular mechanisms of the lethality of hybrid males in crosses between Drosophila melanogaster and sister species. Here, I highlight our discovery of the role of rapidly evolving DNA damage-induced cell cycle checkpoints and DNA replication licensing machinery in hybrid inviability. We propose a testable cell biological model where hybrid lethality is caused by cells attempting to divide before their genomes are fully replicated. Second, we aim to understand the molecular mechanisms of meiotic drive and hybrid sterility in very young subspecies of Drosophila pseudoobscura. Here, I highlight our discovery of the existence of male germline checkpoints and a rapidly evolving non-coding RNA as the basis of drive and sterility. Third, we aim to understand the genetic and molecular basis of meiotic drive in the selfish Sex-Ratio chromosome in D. pseudoobscura. Here, I highlight our discovery of the involvement of rapidly evolving meiotic cohesin and dynein as the genetic basis of meiotic drive. We propose that a failure to properly pair and segregate the Y- chromosome during meiosis is the molecular mechanism of drive. Each of these research directions involves the development of innovative genetic mapping methods and systematically dissecting phenotypes generated by evolution down to their cellular roots; each of these directions has led us to original discoveries involving fundamental cellular processes. Through the unification of the fields of evolutionary genomics and cell & developmental biology, our research program is providing exciting advances in solving long-standing and fundamental problems in biology.