Recombination, Dominance, and Selection on Amino Acid Mutations

这项研究试图了解基因重组和显性如何改变自然选择对替换和沉默突变的影响。一般来说，自然选择对替换突变的作用更强。通过对两个密切相关物种中每个物种的多个基因副本进行测序，可以记录物种内部和物种之间沉默和替换突变的变异量(称为麦克唐纳-克莱特曼测试)。为了验证基因重组和显性程度改变自然选择有效性的假设，将从果蝇、黑腹果蝇和拟果蝇的核基因中收集新的DNA序列数据，这些基因位于很少或没有重组的区域。这些数据将与来自高重组区域的现有数据进行比较。显性的问题将通过获取X染色体上的低重组基因和第四染色体上的低重组基因来解决，X染色体上的低重组基因在雄性是单倍体，而第四染色体上的低重组基因在两性中都是二倍体。虽然已经在X染色体和第4染色体上进行了DNA变异的研究，但在这方面还没有专门关注蛋白质编码基因突变的研究。果蝇的染色体提供的遗传背景意味着，这些数据很可能对所有生物都是通用的，包括人类。由于DNA突变是所有遗传变异的最终来源，了解遗传因素如何改变自然选择消除有害突变和保留有益突变的能力，对于保护遗传生物多样性和人类群体的遗传健康具有普遍意义。

9981497RandThis research seeks to understand how genetic recombination and dominance can alter the effects of natural selection on replacement and silent mutations. In general, natural selection acts more strongly on replacement mutations. By sequencing many copies of a gene from each of two closely related species, one can document the amount of variation within, and between, species for silent and replacement mutations (known as the McDonald-Kreitman test). To test the hypothesis that levels of genetic recombination and dominance alter the effectiveness of natural selection, new DNA sequence data will be collected from nuclear genes that lie in regions experiencing little or no recombination in the fruit flies, Drosophila melanogaster and D. simulans. These data will be compared to existing data from regions of high recombination. The issue of dominance will be addressed by obtaining data from low recombination genes on X-chromosome, which is haploid in males, and low recombination genes on the fourth chromosome, which is diploid in both sexes. While studies of DNA variation have been conducted on the X- and 4th chromosomes, no studies have specifically focused on mutations in protein-coding genes in this context. The genetic contexts provided by the chromosomes of Drosophila mean that the data are very likely to be general for all organisms, including humans. Since mutations in the DNA are the ultimate source of all genetic variation, understanding how genetic factors can alter natural selection's ability to eliminate deleterious mutations and preserve beneficial mutation is of general significance to the preservation of genetic biodiversity and the genetic health of the human population.