Evolution of Dimorphic Sex Chromosomes

提出的研究测试穆勒的棘轮假说，该假说涉及二态性染色体的进化。X和Y性染色体的独特组织是导致许多形式的遗传性疾病表达的性别特异性差异的原因。X性染色体在适应过程中似乎也起着特别重要的作用，因为：1)隐性有益突变的表达水平提高，以及2)与两性二态性相关的性状的一种性别特异性基因表达形式。拟议的研究将扩展先前的工作，该工作已证明穆勒棘轮过程可以在实验室中使用果蝇（普通果蝇）模型系统进行有效研究。影响穆勒棘轮过程运行的因素有：突变、选择、抽样误差和重组。这些因素还决定了在人类和其他人群中维持的致病突变库的大小。拟议的研究将使我们能够更好地了解我们自身有害突变库的动态。采用D. melanogaster模型系统研究了Muller棘轮过程在主要参数变化下的运行速率响应；有效种群大小和重组的存在/不存在。这是通过构建巨大的染色体来完成的，这些染色体被迫像原始的X（重组）或Y（非重组）性染色体一样分离，然后测量有害突变的积累速度。

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.