Variation of D. melanogaster chromosome 4

描述（由申请人提供）：本研究的目的是研究进化的力量，管理不寻常的变异的D。黑腹果蝇第四染色体是我们最近发现的。 长期以来，这条染色体一直被视为自然选择如何导致低重组基因组区域中的低种内变异的典型教科书示例。我们的初步工作表明，以前的结论，即整个4号染色体窝藏低变异是不正确的，不应再作为一个范例。我们在D. melanogaster和simulans。将追求以下目标。(1)使用Monte Carlo模拟的基础上的合并过程与选择和重组，我们将研究一个理论上的人口遗传过程与低平均重组率在整个染色体，但与零星的重组热点。我们期望这一理论分析将揭示重组和变异之间的关系。(2)为了确定染色体上高变异区的长度，我们将描述自然群体中D.第四染色体。(3)比较D. melanogaster与其他兄弟物种中相应区域的序列差异，我们将研究D. simulans和D.日本料理。最后，使用这些理论结果和变异数据，我们将测试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。我们还将描述斯芬克斯基因的变异和进化，这是一个最近起源于D。黑腹果蝇第四染色体，进行结构和表达分析，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.