Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Harmit Malik, PhD
Member, Division of Basic Sciences, Fred Hutchinson Cancer Research Center
Investigator, Howard Hughes Medical Institute
Affiliate Professor, Department of Genome Sciences, University of Washington School of Medicine

Chromosome segregation is essential for the faithful transmission of genetic information to daughter cells during cell division. In eukaryotes, accurate chromosome segregation relies on specific chromosomal regions called centromeres, which recruit components of the proteinaceous kinetochore complex. This complex mediates spindle attachments, which ensure high-fidelity segregation of chromosomes or chromatids during meiosis and mitosis. This basic mechanism for chromosome segregation is highly conserved across eukaryotes. In yeast, flies, mice and plants, catastrophic defects in chromosome segregation and lethality result from deletions of the specialized histone H3 variant CenH3, which is the foundational protein of the kinetochore. First identified as Cenp-A in mammals, CenH3 replaces canonical H3 in centromeric nucleosomes. Despite its essential role in eukaryotic chromosome segregation, our evolutionary analyses have revealed unexpectedly rapid evolution of CenH3 in plants and animals. To address why centromeric DNAs and proteins might be subject to relentless evolutionary innovation, we previously proposed the ‘centromere-drive’ hypothesis. Under our hypothesis, centromeric DNA changes that favor the recruitment of centromeric proteins lead to preferential transmission through female meiosis in plants and animals, in which only one of four meiotic products is chosen to be the egg pronucleus. This female meiotic drive could incur a cost to male fertility, and would therefore select for suppressors that can restore meiotic centromere parity and thus male fertility. We propose that centromeric and heterochromatin DNA-binding proteins may be such suppressors of centromere-drive. Thus, meiotic battles at the centromeres may rapidly shape repertoires of centromeric proteins. Such genetic conflicts could also give rise to reproductive isolation (infertility, inviability) in crosses between closely related species.