Variation of D. melanogaster chromosome 4

描述(申请人提供)：这项研究的目的是研究控制我们最近发现的黑腹蛇第四染色体异常变异的进化力量。很长一段时间以来，这个染色体一直被视为一个经典的教科书例子，说明自然选择如何导致低重组基因组区域的物种内低变异。我们的初步工作表明，先前关于整个4号染色体存在低变异的结论是不正确的，不应再作为一种范式。我们在黑腹鼠和拟南虎的这条染色体的大块中发现了高水平的核苷酸变异。将实现以下目标。(1)利用基于选择和重组的聚合过程的蒙特卡罗模拟，我们将研究一个理论上的群体遗传过程，该过程与整个染色体的平均重组率低有关，但有零星的重组热点。我们期望这一理论分析将为重组和变异之间的关系提供新的线索。(2)为了确定染色体高变异区的长度，我们将表征自然群体中黑腹果蝇第四染色体常染色质区域的多态分布。(3)为了将黑腹毛虫的高变异区与其他近缘物种的相应区域进行比较，我们将研究黑腹毛虫和雅库巴毛虫的序列变异。最后，利用这些理论结果和变异数据，我们将检验几个可能解释染色体变异和进化的假说：选择性扫描、背景选择、平衡选择和中性。我们还将通过结构和表达分析来表征狮身人面像基因的变异和进化，并探讨其在染色体进化中的潜在作用。这些研究将大大增加对果蝇第四染色体进化遗传学的理解。

DESCRIPTION (provided by applicant): The objective of this research is to study evolutionary forces that govern unusual variation of the D. melanogaster fourth chromosome uncovered recently by us. For a long time, this chromosome has been viewed as a canonical textbook example of how natural selection can result in low within-species variation in a genome region of low recombination. Our preliminary work has indicated that the previous conclusion that the entire chromosome 4 harbors low variation is incorrect and should not be taken as a paradigm any more. We have found a high level of nucleotide variation in large blocks of this chromosome in D. melanogaster and simulans. The following objectives will be pursued. (1) Using Monte Carlo simulations based on the coalescent process with selection and recombination, we will investigate a theoretical population genetic process associated with a low average recombination rate in the whole chromosome but with sporadic recombination hot spots. We expect that this theoretical analysis will shed new light on the relationship between recombination and variation. (2) To determine the length of the high variation region in the chromosome, we will characterize the polymorphism distribution in natural populations in whole euchromatin regions of the D. melanogaster fourth chromosome. (3) To compare the high variation region of D. melanogaster with the corresponding region in other sibling species, we will investigate sequence variation in D. simulans and D. yakuba. Finally, using these theoretical results and variation data, we will test several hypotheses that might explain the variation and evolution of the chromosome: selective sweep, background selection, balancing selection, and neutrality. We will also characterize the variation and evolution of the sphinx gene, a gene that recently originated on the D. melanogaster fourth chromosome, with structural and expression analysis, and investigate its potential role in the evolution of the chromosome. These studies should add significantly to the understanding of the evolutionary genetics of the Drosophila fourth chromosome.