Study of positive selection in yeast

Fred Hutchinson Cancer Research Center, Seattle WA

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Abstract

DESCRIPTION (provided by applicant): Positive selection of genes implies evolution towards new or diversified function. The Saccharomyces cerevisiae genome will be screened computationally, with a sliding window analysis of ka/ks values, for genes evolving under positive selection. Initial results reveal 32 characterized genes evolving under positive selection, 10% of which function in non-homologous end-joining (NHEJ). It is counter-intuitive to find genes involved in protecting fundamental genome integrity subject to diversifying evolutionary pressures. NHEJ functions in DNA repair and has been linked to genetic translocations and hypermutation, both of which are detrimental to human health. NHEJ proteins from different species will be assayed in vivo to determine how and why their functions have diverged. The hypothesis that Ty1 retrotransposons are in conflict with NHEJ components, and cause their adaptive evolution, will be tested. In addition, the functional "cost" of the adaptive evolution of NHEJ components will also be tested. This will be the first detailed characterization of the positive selection landscape of the yeast genome (or any genome for that matter) and the first study of NHEJ components evolving under positive selection.