INVESTIGATING THE MALE-DRIVEN EVOLUTION HYPOTHESIS USING GENOME WIDE POINT MUTATIONS IN HUMAN ALU REPEATS

Background: There is substantial evidence that replication-based nucleotide substitutions in primatesoccur more frequently in males than in females. There has been disagreement about the extent of this disparity.The human Alu repeats provide an ideal mechanism to further investigate the degree of replication-based error byproviding tighter statistical boundaries on the male-to-female mutation ratio, α, in humans. Results: We analyzepatterns of point mutations in Alu repeats across the entire human genome in order to elucidate the processes ofmutation and fixation. This analysis provides substantial statistically bounded support for the accumulation ofmore point mutations in the Y chromosome compared to the X chromosome. We report a 99.99% confidenceinterval for human α between 1.280 and 1.289. Our results suggest that compared with eggs, sperm tend to carrya greater number of point mutations accumulated primarily during the production of gametes. Conclusion: Ourresults suggest that although mutation may be primarily replication driven (as previous studies suggest) the observedvalue of α does not exceed the threshold necessary to conclude that contributions of replication independentfactors are negligible.