The proposed research tests the Muller's ratchet hypothesis which concerns the evolution of dimorphic sex chromosomes. The distinctive organization of the X and Y sex chromosomes is responsible for sex-specific differences in the expression of many forms of hereditary disease. The X sex chromosome also appears to play a particularly important role in the process of adaptation, due to: 1) an enhanced level of expression of recessive, beneficial mutations, and 2) a form of sex specific gene expression for traits associated with sexual dimorphism. The proposed research will extend previous work which has demonstrated that the Muller's ratchet process can be effectively studied in the laboratory using a Drosophila melanogaster (common fruit fly) model system. The factors that affect the operation of the Muller's ratchet process are: mutation, selection, sampling error, and recombination. These factors also determine the size of the reservoir of disease-causing mutation that are maintained in human and other populations. The proposed research will permit us to better understand the dynamics of our own reservoir of deleterious mutations. The research used a D. melanogaster model system to study the rate of operation of the Muller's ratchet process in response to manipulative changes in its major parameters; the effective population size, and the presence/absence of recombination. This is accomplished by constructing giant chromosomes that are forced to segregate like either a primitive X (recombining) or Y (non-recombining) sex chromosomes and then measuring the rate of accumulation of deleterious mutations.
