Recombination, Dominance, and Selection on Amino Acid Mutations

9981497 rand本研究旨在了解基因重组和显性如何改变自然选择对替代和沉默突变的影响。一般来说，自然选择对替代突变的作用更大。通过对两个亲缘关系密切的物种中的每个物种的一个基因的多个拷贝进行测序，人们可以记录物种内部和物种之间的沉默突变和替代突变的变异量（称为麦当劳-克雷特曼测试）。为了验证基因重组和显性水平改变自然选择有效性的假设，新的DNA序列数据将从果蝇、黑腹果蝇（Drosophila melanogaster）和拟蝇（d.s simulans）中处于很少或没有重组区域的核基因中收集。这些数据将与来自高重组区域的现有数据进行比较。从雄性单倍体的x染色体上的低重组基因和雌雄双倍体的第四染色体上的低重组基因中获得显性问题。虽然已经对X和4号染色体进行了DNA变异的研究，但在这种情况下，没有研究专门关注蛋白质编码基因的突变。果蝇染色体提供的遗传背景意味着，这些数据很可能适用于包括人类在内的所有生物。由于DNA的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种群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.