The molecular origins and implications of genomic structural variation in deer mice

Abstract

Understanding the origins and evolution of genome architecture is a central goal in biology. Nonetheless, genomic structural variation within species remains poorly characterized in natural populations and the molecular mechanisms underlying variation in genome architecture are largely obscure. Here, I apply theory of genetic conflict, state-of-the-art sequencing techniques and recently developed bioinformatics methods to investigate the origins of genome architecture and characterize genomic structural variation in the deer mouse (Peromyscus maniculatus), a mammalian model system for studying natural variation. In Chapter 1, I show that endogenization and subsequent invasion of divergent retroviruses ultimately gave rise to a unique genomic repeat landscape in the deer mouse relative to nearly all other studied mammals. In Chapter 2, by sequencing and comparing chromosome-level genome assemblies within deer mouse populations, I elucidate how various genomic repeats contribute to the formation of massive chromosomal rearrangements resulting in widespread intraspecific karyotype variation. Finally, in Chapter 3, I use newly developed pangenomic methods to characterize structural variation in ecologically and biogeographically diverse deer mouse populations, revealing striking gene copy number variation with likely implications in adaptation. Together this work characterizes several novel patterns of genome evolution in a mammal, providing important insight into the processes that give rise to variation in mammalian genome structure.