Dissertation Research: Using Patterns of Nucleotide Diversity to Distinguish Between Modes of Selection in Very Low Recombining Regions of the Drosophila Genome

9701114查尔斯沃斯的遗传物质在母系和父系来源的同源染色体之间通过交换过程进行交换。基因DNA序列的种内变异性水平与基因经历交叉的频率有关。果蝇的四号染色体没有交叉，它的基因几乎没有变异性。这为检验关于交叉和可变性之间的关系的两个主要假说提供了机会。在第一种假设下，在没有交叉的情况下，变异性被消除了，因为当它在整个物种中传播时，一个选择性有利的变异会把染色体上的所有基因都拖到一起。可变性的恢复依赖于新的突变，而新的突变必然是罕见的。在第二种假设下，变异性减少了，因为选择不断地消除整个染色体上的有害突变；稀有和常见变异的相对丰度应该几乎不受影响。这些假说将通过使用DNA测序技术检查该染色体上基因的罕见变异和常见变异的比例来检验。这项研究将阐明影响自然种群多样性水平的遗传机制。这对保护生物学和人类变异的遗传学以及对基本生物过程的知识具有广泛的影响。

9701114 Charlesworth Genetic material is exchanged between maternally and paternally derived homologous chromosomes, by the process of crossing over. The level of within-species variability in the DNA sequence of a gene is related to the frequency with which the gene experiences crossing over. Chromosome four of the fruitfly Drosophila melanogaster lacks crossing over, and its genes show little variability. This provides an opportunity to test two major hypotheses about the relation between crossing over and variability. Under the first hypothesis, variability is eliminated in the absence of crossing over because a selectively favorable variant drags all genes on the chromosome along with it, as it spreads through the species. Restoration of variability depends on new mutations, which are necessarily rare. Under the second hypothesis, variability is reduced because selection continually eliminates harmful mutations all along the chromosome; the relative abundance of rare versus common variants should be little affected. These hypotheses will be tested by examining the proportions of rare versus common variants at genes on this chromosome, using DNA sequencing technology. This research will shed light on the genetic mechanisms affecting diversity levels in natural populations. This has broad implications for conservation biology and the genetics of human variation, as well as for knowledge of fundamental biological processes.