DNA Variability and Natural Selection in House Mice and Humans

种群遗传学的一个中心目标是了解决定生物自然种群中遗传变异的数量和分布的力量。该项目的主要目标是在小鼠和人类种群的DNA序列变异模式中寻找自然选择的证据。第二个目标是确定两种选择形式的相对重要性：新的有益突变的传播和种群中有害突变的消除。分子技术和统计分析的最新改进将用于测序和分析DNA变异模式，包括家鼠（家鼠）的20个基因和人类的10个基因，以及与家鼠密切相关的两种小鼠（Mus spretus和Mus caroli）和与人类密切相关的两种灵长类动物（猩猩和普通黑猩猩）。来自X染色体和其他几条染色体的基因将被测序。这项工作的一个重要目的是确定每个基因的遗传变异量与重组率之间的关系（个体中基因的两个拷贝之间的遗传混合量）。对果蝇的研究和对小鼠的初步研究表明，重组越多的基因就越容易变异。这有重要的含义；例如，对估计一个物种的遗传变异性感兴趣的保护生物学家将需要对具有高重组率和低重组率的基因进行取样。该项目将深入了解影响自然界遗传变异数量和分布的过程。这不仅对保护生物学很重要，而且对理解任何生物进化变化的遗传基础也很重要。此外，对人类的研究将记录世界不同地区内部和之间的遗传变异数量，并将为现代人类的起源和迁徙提供重要线索。

9628942 Nachman A central goal of population genetics is to understand the forces that determine the amount and distribution of genetic variation in natural populations of organisms. The primary goal of this project is to look for evidence of natural selection in patterns of DNA sequence variation in populations of mice and humans. The second objective is to determine the relative importance of two forms of selection: the spread of new beneficial mutations, and the elimination of deleterious mutations from populations. Recent improvements in molecular techniques and statistical analyses will be used to sequence and analyze patterns of DNA variation, in 20 genes in house mice (Mus domesticus) and 10 genes in humans, as well as in two species of mice (Mus spretus and Mus caroli) closely related to the house mouse and in two primates (Orangutan and Common chimpanzee) closely related to humans. Genes from the X chromosome and from several other chromosomes will be sequenced. An important aim of this work is to determine the relationship between the amount of genetic variation at each gene and the rate of recombination (the amount of genetic mixing between the two copies of a gene in individuals). Work in fruit flies and preliminary work in mice suggests that genes with more recombination are more variable. This has important implications; for example, conservation biologists interested in estimating genetic variability in a species will need to sample genes with both high and low recombination rates. This project will provide insight into the processes affecting the amount and distribution of genetic variation in nature. This is essential not only for conservation biology but also for understanding the genetic basis of evolutionary change in any organism. Moreover, the work on humans will document the amount of genetic variability within and between different regions of the world and will provide important clues to the origins and migrations of modern humans.