Genetic and developmental mechanisms of hybrid dysfunction in house mice (Mus musculus musculus and M. m. domesticus)

: (Alternative Format Thesis)

Abstract

It is one hundred and sixty-two years on from the first publication of Darwin’s ‘On the Origin of Species’ and the mechanisms through which new species arise are still not fully understood. One of the key steps in the process of speciation is reproductive isolation, and an important reproductive barrier is postzygotic isolation. This occurs when hybrid offspring are less fit or less healthy than the parental species, leaving them unable to compete. Whilst many writings have been dedicated to how postzygotic isolation occurs, there remain many fundamental questions about the mechanisms at play. Here we aim to further our understanding of intrinsic postzygotic isolation mechanisms using the house mouse hybrid zone as a model system. The house mouse (Mus musculus) forms a stable hybrid zone in central Europe, where two subspecies (M. m. domesticus and M. m. musculus) meet and interbreed. This thesis explores the mechanisms that underlie reproductive isolation phenotypes observed in the hybrids of these two subspecies. There is a specific focus on hybrid male sterility, a commonly observed phenotype in the hybrid zone, and imprinting imbalances, an as-yet undocumented mechanism of isolation in this hybrid system. In a genome-wide association study using wild-derived inbred lines, we identify novel regions associated with male fertility phenotypes, as well as further validating previously identified regions. We also observe the progression of spermatogenesis, from the onset of meiosis in a range of mouse strains that represent different states of hybrid fertility and identify key time points at which break down occurs, as well as identifying chromosomal regions likely to harbour hybrid male sterility genes. Finally, we provide the first evidence of a role for imprinting imbalances in the segregation occurring in the house mouse hybrid zone, through the identifying parent-of-origin growth effects in embryos and placentae.

Date of Award	27 Apr 2022
Original language	English
Awarding Institution	University of Bath
Supervisor	Leslie Turner (Supervisor) & Jason Wolf (Supervisor)