Dynamics of Mutator Evolution: An Experimental Study

9981518 Sniegowski这个项目将研究为什么细菌种群中基因突变的高发生率和持续性。PI先前已经记录了在实验室中繁殖的大肠杆菌群体中由变构基因引起的高突变率的起源和持续性。本项目的三个目标是：1）理解为什么突变基因是成功的; 2）研究突变基因在种群中的动力学; 3）记录这些种群中突变基因产生的DNA序列变化。目标1和2将通过实验室实验来实现，其中E.携带突变基因的大肠杆菌细胞与正常的大肠杆菌细胞竞争。目标3将通过突变基因的DNA测序来实现。由于突变是遗传变异的最终来源，阐明突变率是如何建立和维持的，对我们理解遗传学和进化具有基础性的重要意义。但也存在着重大的社会影响：突变基因与细菌的致病性和人类的癌症有关。PI已经表明，这些突变基因和他的研究中的突变基因是由相同的一般遗传途径中的缺陷系统化的，进一步的研究表明，类似的群体水平过程可能涉及实验室和自然界。因此，该项目可能会在这些具有社会重要性的领域提供重要的见解。

9981518SniegowskiThis project will study why high rates of genetic mutation ariseand persist in bacterial populations. The PI has previously documented theorigin and persistence of high mutation rates caused by mutator genes inpopulations of Escherichia coli that have been propagated in thelaboratory. The three goals of the current project are: 1) to understandwhy mutator genes are successful; 2) to study the dynamics of mutator genesin populations; and 3) to document the DNA sequence changes that give riseto mutator genes in these populations. Goals 1 and 2 will be achievedthrough laboratory experiments in which E. coli cells bearing mutator genesare competed against their normal counterparts. Goal 3 will be achieved byDNA sequencing of mutator genes. Because mutation is the ultimate source of genetic variation,elucidating how mutation rates are established and maintained is offundamental importance to our understanding of genetics and evolution. Butsubstantial societal implications exist as well: Mutator genes have beenassociated with pathogenicity in bacteria and with cancer in humans. The PIhas shown that these mutator genes and the mutators in his study systemarise from defects in the same general genetic pathway, and furtherresearch has suggested that similar population-level processes are likelyto be involved in the laboratory and in nature. This project is thereforelikely to contribute significant insights in these areas of societalimportance.