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Tissue-specific codon usage in mouse

Posted on:2012-04-13Degree:D.Sc.(Econ/BusAdmType:Thesis
University:University of Ottawa (Canada)Candidate:Palidwor, Gareth AFull Text:PDF
GTID:2460390011464343Subject:Biology
Abstract/Summary:
Codon usage bias is due to a combination of biased mutation and selection effects. Isochore-related GC mutational bias has been shown to be the dominant cause of tissue-specific codon bias in adult human tissues and limited evidence for translational selection has been shown. This thesis is a comprehensive evaluation of the relative contribution of selection and mutation to variation in codon usage among different mouse embryonic tissues.;In mouse, the usage of some G-ending codons decreases with increasing GC bias, while all other G and C-ending codons increase. To understand this counterintuitive observation, we generate a continuous-time Markov chain model of GC-biased synonymous substitution which explains qualitative usage patterns of all codons, including non-linear and sometimes non-monotone codon usage in isoleucine, arginine and leucine. This effect is universal, extending to mouse and human genes as well as plant and prokaryotic genomes.;This work enriched our understanding of the codon-anticodon adaptation theory and extended it to the level of tissue-specific genes. The result suggests the possibility of tissue-specific tRNA pools mediating tissue-specific codon-anticodon adaptation. The methods developed in the thesis can be easily extended to characterize this previously little explored facet of codon-anticodon adaptation.;Through a detailed analysis of tissue-specific codon usage in relation to gene expression and gene location of mouse embryonic tissue-specific genes, I found that translational selection is partially responsible for some differences in codon usage among tissue-specific genes. This observation indicates profound impact of selection favouring codon-anticodon adaptation. The characteristic GC biases of tissue-specific gene sets are shown not to be caused by their clustering on the same isochore. Tissue-specific genes are no more clustered on the genome than randomly selected genes.
Keywords/Search Tags:Codon usage, Tissue-specific, Mouse, Selection, Bias
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