Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.650436
Title: Studies of synonymous codon evolution in mammals
Author: Eyre-Walker, Adam C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1992
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Abstract:
Although tremendous progress has been made in many other groups, the forces and factors which affect synonymous codon use in mammals remain something of a mystery. At least some of the differences in codon usage between mammalian genes can be summarised in terms of composition: within any one species some genes have very low G+ C contents (< 30%) and others very high G+ C content (> 90&37), with the majority lying somewhere in between. The very simplicity of this trend and the fact that this composition is correlated to that of introns and isochores suggests that the differences in synoymous codon use may be the result of variation in the pattern of mutation across the genome. This hypothesis is examined by considering the three most likely ways in which the mutation pattern might vary across the genome: (1) temporal changes in the performance of the replicative machinery; (2) variation in the efficiency of DNA repair; and (3) variation in the frequency of gene conversion across the genome. Evidence is found against all these hypotheses. Principally none of them predict the silent substitution rate to be related to G+ C content in the manner which is observed. Furthermore the lack of any discernible difference between the silent site G+ C contents of early and late replicating genes, and the very small parameter range over which DNA repair can generate large differences in synonymous codon use, support the conclusions that replication and repair, respectively, are not responsible for the codon use of mammalian genes. It is therefore suggested that selection might act upon synonymous codon use. However an analysis of codon usage within genes suggests that selection of the type commonly found in other groups, selection upon tRNA interaction, is not operative in mammals. It is tentatively suggested that selection upon mRNA secondary structure might be the responsible agent. Some of the results obtained also have implications for the maintenance of isochores. Since the G+ C contents of isochores and silent sites are correlated, the lack of any distinction with respect to composition between early and late replicating genes suggests that the differences in isochore G+ C content are not cuasd by DNA replication. However it is hypothesised that variation in the frequency of recombination can provide a very elegant explanation of the differences in isochore G+ C contents, and the relationship between gene density and isochore G+ C content.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.650436  DOI: Not available
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