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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM074299-02
Application #
7115728
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Haynes, Susan R
Project Start
2005-09-01
Project End
2007-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Sawyer, Sara L; Emerman, Michael; Malik, Harmit S (2007) Discordant evolution of the adjacent antiretroviral genes TRIM22 and TRIM5 in mammals. PLoS Pathog 3:e197
Sawyer, Sara L; Malik, Harmit S (2006) Positive selection of yeast nonhomologous end-joining genes and a retrotransposon conflict hypothesis. Proc Natl Acad Sci U S A 103:17614-9