BIASES IN THE RATES AND PATTERNS OF MOLECULAR EVOLUTION

Ochman实验室的长期目标之一是调查 细菌序列进化过程的潜在因素。一个基本 分子进化生物学的前提是突变发生在 在整个基因组中是随机的， 核苷酸替换是自然选择的直接结果。 然而，一些证据表明情况并非如此。 突变是通过DNA复制过程中的错误而产生的; 复制互补链的机制不同， 两条链上的突变率可能不同。在 此外，在基因突变的频率上也存在差异。 DNA的编码和非编码链，这表明某些过程， 例如对密码子使用、脱氨基事件和转录的选择， 偶联修复，靶向互补链之一。 拟议研究的目标是确定是否领先和 落后的DNA链具有不等的突变率，为了确定 基因组转录部分突变对称性的来源。 这些问题将通过两种相辅相成的方法加以审查： 基因突变率的实验分析引入到 染色体在相反的方向，和分析的取代， 编码潜力和水平不同的染色体区域 的表达。累积起来，这些研究将确定相对于 复制错误和DNA损伤在产生天然的 在种群中观察到的遗传变异。

One of the long-term goals of the Ochman laboratory is to investigate factors underlying process of sequence evolution in bacteria. A basic premise of molecular evolutionary biology is that mutations occur at random throughout the genome and that variation in the pattern of nucleotide substitutions is the direct result of natural selection. However, several lines of evidence suggest that this is not the case. Mutations arise through errors during the DNA replication; and because the mechanisms for replicating the complementary strands differ, it is possible for the rates of mutations to differ on the two strands. In addition, there are differences in the frequencies of mutations of the coding and non-coding strands of DNA, suggesting that certain processes, such as selection on codon usage, deamination events and transcription- coupled repair, are targeted to one of the complementary strands. The goals of the proposed research are to determine if the leading and lagging strands of DNA have unequal mutation rates, and to ascertain the source of mutational symmetries in transcribed portions of the genome. These issues will be examined by two complementary approaches: an experimental assay of mutation rates in genes introduced into the chromosome in opposite orientations, and an analysis of substitutions in chromosomal regions that differ with respect to coding potential and level of expression. Cumulatively, these studies will establish the relative roles of replication errors and DNA damage in generating the naturally- occurring genetic variation observed in populations.