Dissertation Research: Using Patterns of Nucleotide Diversity to Distinguish Between Modes of Selection in Very Low Recombining Regions of the Drosophila Genome

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9701114 Charlesworth Genetic material is exchanged between maternally and paternally derived homologous chromosomes, by the process of crossing over. The level of within-species variability in the DNA sequence of a gene is related to the frequency with which the gene experiences crossing over. Chromosome four of the fruitfly Drosophila melanogaster lacks crossing over, and its genes show little variability. This provides an opportunity to test two major hypotheses about the relation between crossing over and variability. Under the first hypothesis, variability is eliminated in the absence of crossing over because a selectively favorable variant drags all genes on the chromosome along with it, as it spreads through the species. Restoration of variability depends on new mutations, which are necessarily rare. Under the second hypothesis, variability is reduced because selection continually eliminates harmful mutations all along the chromosome; the relative abundance of rare versus common variants should be little affected. These hypotheses will be tested by examining the proportions of rare versus common variants at genes on this chromosome, using DNA sequencing technology. This research will shed light on the genetic mechanisms affecting diversity levels in natural populations. This has broad implications for conservation biology and the genetics of human variation, as well as for knowledge of fundamental biological processes.