This research seeks to understand how genetic recombination and dominance can alter the effects of natural selection on replacement and silent mutations. In general, natural selection acts more strongly on replacement mutations. By sequencing many copies of a gene from each of two closely related species, one can document the amount of variation within, and between, species for silent and replacement mutations (known as the McDonald-Kreitman test). To test the hypothesis that levels of genetic recombination and dominance alter the effectiveness of natural selection, new DNA sequence data will be collected from nuclear genes that lie in regions experiencing little or no recombination in the fruit flies, Drosophila melanogaster and D. simulans. These data will be compared to existing data from regions of high recombination. The issue of dominance will be addressed by obtaining data from low recombination genes on X-chromosome, which is haploid in males, and low recombination genes on the fourth chromosome, which is diploid in both sexes. While studies of DNA variation have been conducted on the X- and 4th chromosomes, no studies have specifically focused on mutations in protein-coding genes in this context.
The genetic contexts provided by the chromosomes of Drosophila mean that the data are very likely to be general for all organisms, including humans. Since mutations in the DNA are the ultimate source of all genetic variation, understanding how genetic factors can alter natural selection's ability to eliminate deleterious mutations and preserve beneficial mutation is of general significance to the preservation of genetic biodiversity and the genetic health of the human population.
