Presenter: John Didion
John Didion1,2,3, Dan M Gatti4, Andrew P Morgan1,2,3, Timothy A Bell1,2,3, Ling Bai5, James J Crowley1, John E French6, Thomas R Geiger5, Alison H Harrill7, Kent Hunter5, Kenneth Paigen4, Petko M Petkov4, Daniel Pomp1, Karen L Svenson4, Elissa J Chesler4, Gary Churchill4, Fernando Pardo-Manuel de Villena1,2,3 1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 2Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 3Carolina Center for Genome Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 4Center for Genome Dynamics, The Jackson Laboratory, Bar Harbor, ME, USA 5Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, USA 6Laboratory of Respiratory Biology, National Institute of Environmental Sciences, NIH, Research Triangle Park, NC, USA 7The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA
Statistically significant departures from the expected Mendelian inheritance ratios (transmission ratio distortion, TRD) have been observed in interspecific crosses in plant and animal species, including mice and humans. A variety of mechanisms may give rise to TRD, including differential viability of embryos or gametes of either sex, and unequal segregation of chromosomes during female meiosis (meiotic drive). TRD can have profound consequences on allele frequencies, especially in closed-breeding groups such as the CC and DO. We used CC and DO genotype data across more than 20 generations to identify and characterize maternal meiotic drive. We observed significant and reproducible TRD in favor of WSB/EiJ alleles within an ~8 Mb region of chromosome 2, approximately 50 cM from the centromere. WSB/EiJ alleles are quickly sweeping the candidate region in the DO; we have implemented a strategy to purge these alleles and recover the diversity at this locus. Analysis of transmission frequency data in the CC, DO and several other crosses has shown that TRD occurs exclusively through the female germline. These results strongly indicate a mechanism of unequal chromatid segregation at the second meiotic division. The reproducibility of the CC and the existence of multiple chromosomes that are recombinant in our region of interest provide us the opportunity to develop a model system in which to characterize the cellular and molecular mechanism underlying meiotic drive. This novel meiotic drive system, along with the select others that are known, suggests that exceptions to Mendel’s First Law are more common than previously thought.