Variation of D. melanogaster chromosome 4

描述（由申请人提供）：本研究的目的是研究控制我们最近发现的D. melanogaster第四染色体异常变异的进化力量。很长一段时间以来，这条染色体一直被视为自然选择如何在低重组的基因组区域导致低物种内变异的典型教科书。我们的初步工作表明，先前关于整个4号染色体具有低变异的结论是不正确的，不应再作为范式。我们已经在黑腹海蛞蝓和拟鱼的这条染色体的大片段中发现了高水平的核苷酸变异。将追求下列目标。(1)采用蒙特卡罗模拟方法，对具有选择和重组的聚结过程进行了研究，研究了一个整体染色体平均重组率较低但存在零星重组热点的理论群体遗传过程。我们期望这一理论分析将对重组与变异之间的关系提供新的启示。(2)为了确定染色体高变异区域的长度，我们将对黑腹龙第4染色体整个常染色质区域的多态性分布进行表征。(3)为了比较黑腹龙种的高变异区与其他兄弟种的高变异区，我们将研究拟象龙种和雅库巴龙种的序列变异。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设：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描述sphinx基因的变异和进化，sphinx基因是一个最近起源于D. melanogaster第四染色体的基因，并研究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.