Gender Specific Impact of Replication and Recombination on Rodent Intron Evolution

Abstract

Mutation rate variability has been widely observed across mammalian genomes butthe underlying causes are not yet fully understood. This thesis attempts to explainthis variation, as assayed by the substitution rate of putatively neutral sites, acrossrodent genomes at three scales: genic, inter-autosomal and between chromosometypes. It was shown that the method commonly employed to estimate the extent ofmale-bias in the mutation rate is flawed, suggesting that inter-chromosomal variationin mutation rates is not solely due to differences in the number of replications theyundergo in each germ-line. Two novel models were proposed that incorporated anadditional recombination-associated parameter to explain why, contrary to the theoryof male-driven evolution, the autosomes evolve faster than the Y-chromosome. Asnumber of replications could not fully account for mutational variability at any scale,the impact of the time during S-phase when replication occurs was explored.Differential timing of replication was shown to explain both inter-genic and someinter-autosomal variation in intronic substitution rates, with later replicatingsequences evolving faster. However, controlling for different replication times failedto account for why number of replications could not explain differences inchromosomal divergence. Further, GC rich sequences were found to evolve slowlybecause they tend to replicate early. Finally, late replicating genes were found tohave high recombination rates in females but low recombination rates in males.These previously unidentified relationships could explain why, owing to sex-specificcovariance with replication timing, the strength of covariance betweenrecombination rate and divergence was underestimated in males and overestimatedin females. It might also explain why female recombination rates, unlike those inmales, do not covary with GC content.

Date of Award	28 Feb 2012
Original language	English
Awarding Institution	University of Bath
Supervisor	Laurence Hurst (Supervisor)