Natural selection and DNA sequence variation in Mus

小鼠的自然选择和 DNA 序列变异

• 批准号: 7010359
• 负责人: MICHAEL W. NACHMAN
• 金额: $ 23.39万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7010359
• 关键词: Mus musculus; animal genetic material tag; animal population genetics; autosome; genetic mapping; genetic screening; genetic strain; genotype; laboratory mouse; linkage disequilibriums; natural selections; nucleic acid sequence; reproduction; sex chromosomes; single nucleotide polymorphism; species difference; statistics /biometry

DESCRIPTION (provided by applicant): With the complete sequence of the mouse genome available, we can now study genetic variation from natural populations in different genomic regions, investigate the forces underlying that variation, and begin to identify functional variants. Significant efforts have gone into the description of single nucleotide polymorphisms (SNPs) among inbred laboratory strains of mice, yet little is known of how this variation relates to population-level variation in the wild. For example, many lab mouse SNPs may represent fixed interspecific differences between Mus domesticus and Mus musculus, while others may represent intraspecific polymorphisms segregating in one or both species. The proposed research will (1) document patterns of nucleotide variation in natural populations of M. domesticus and M. musculus by sequencing 5-10 kb at each of 15 genes on the X chromosome and 15 genes on autosomes and also sequencing these same genes in two closely related species of mice, M. spretus and M. caroli, (2) relate genetic variation in these natural populations to genetic variation among inbred strains by sequencing the same 30 genes in nine commonly used inbred strains and also by genotyping the wild mice for a set of 300 SNPs previously ascertained in inbred strains, (3) document patterns of intraspecific nucleotide polymorphism and interspecific divergence for a set of 12 genes known to be involved in reproduction and chosen as likely targets for selection, (4) provide a large-scale scan for the effects of natural selection by assaying microsatellite variation at 100 markers spaced along the X chromosome and 100 markers on chromosome 1, and (5) sequence a series of windows spaced at regular intervals adjacent to several loci identified as targets of selection from the work described above. The thirty genes on the X chromosome and autosomes will be compared to published polymorphism surveys of these same genes in humans. Because many of these genes are found in different genomic environments in mice and humans, this comparison will provide a direct test of the hypothesis that genomic context is an important determinant of patterns of genetic variation. The proposed research will provide the first comprehensive description of nucleotide variation in natural populations of M. domesticus and M. musculus and will provide a clear picture of the relationship between variation among commonly used inbred strains and variation in natural populations.

描述（由申请人提供）：有了完整的小鼠基因组序列，我们现在可以研究来自不同基因组区域的自然种群的遗传变异，调查这种变异背后的力量，并开始识别功能变异。在实验室小鼠的近交品系中，对单核苷酸多态性（snp）的描述已经付出了巨大的努力，但这种变异与野生种群水平的变异之间的关系却知之甚少。例如，许多实验室小鼠的snp可能代表家鼠和小家鼠之间固定的种间差异，而另一些则可能代表一个或两个物种中分离的种内多态性。拟进行的研究将：(1)通过对X染色体上的15个基因和常染色体上的15个基因分别进行5-10 kb的测序，并对两种亲缘关系密切的小鼠M. spretus和M. caroli的相同基因进行测序，来记录M. domesticus和M. musus自然种群的核苷酸变异模式；(2)通过对9个常用近交系中相同的30个基因进行测序，并对野生小鼠进行基因分型，以确定近交系中已有的300个单核苷酸多态性，从而将这些自然种群的遗传变异与近交系之间的遗传变异联系起来；(3)对12个已知与生殖有关的基因的种内核苷酸多态性和种间差异模式进行记录，这些基因被选为可能的选择目标；(4)通过分析X染色体上的100个标记和1号染色体上的100个标记的微卫星变异，对自然选择的影响进行大规模扫描；(5)对一系列间隔有规则的窗口进行排序，这些窗口与上述工作中确定为选择目标的几个位点相邻。X染色体和常染色体上的30个基因将与已发表的人类这些相同基因的多态性调查进行比较。因为这些基因中的许多是在小鼠和人类的不同基因组环境中发现的，这种比较将为基因组环境是遗传变异模式的重要决定因素这一假设提供直接检验。该研究将首次全面描述家蝇和肌肉家蝇自然种群的核苷酸变异，并将为常用近交系间的变异与自然种群变异之间的关系提供清晰的图像。