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Title: Gender specific impact of replication and recombination on rodent intron evolution
Author: Pink, Catherine
ISNI:       0000 0004 2725 9880
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2012
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Mutation rate variability has been widely observed across mammalian genomes but the underlying causes are not yet fully understood. This thesis attempts to explain this variation, as assayed by the substitution rate of putatively neutral sites, across rodent genomes at three scales: genic, inter-autosomal and between chromosome types. It was shown that the method commonly employed to estimate the extent of male-bias in the mutation rate is flawed, suggesting that inter-chromosomal variation in mutation rates is not solely due to differences in the number of replications they undergo in each germ-line. Two novel models were proposed that incorporated an additional recombination-associated parameter to explain why, contrary to the theory of male-driven evolution, the autosomes evolve faster than the Y-chromosome. As number 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 some inter-autosomal variation in intronic substitution rates, with later replicating sequences evolving faster. However, controlling for different replication times failed to account for why number of replications could not explain differences in chromosomal divergence. Further, GC rich sequences were found to evolve slowly because they tend to replicate early. Finally, late replicating genes were found to have high recombination rates in females but low recombination rates in males. These previously unidentified relationships could explain why, owing to sex-specific covariance with replication timing, the strength of covariance between recombination rate and divergence was underestimated in males and overestimated in females. It might also explain why female recombination rates, unlike those in males, do not covary with GC content.
Supervisor: Hurst, Laurence Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available