Dynamics of Mutator Evolution: An Experimental Study

Sniegowski这个项目将研究为什么高基因突变率在细菌种群中出现并持续存在。PI以前已经证明了突变子基因在已在该实验室繁殖的大肠杆菌种群中引起的高突变率的起源和持久性。目前项目的三个目标是：1)了解突变基因为什么成功；2)研究突变基因在种群中的动态；3)记录导致这些种群中突变基因发生变化的DNA序列变化。目标1和2将通过实验室实验实现，在这些实验中，携带突变子基因的大肠杆菌细胞与正常细胞竞争。目标3将通过突变基因的DNA测序来实现。因为突变是遗传变异的最终来源，阐明突变率是如何建立和保持的，对于我们理解遗传学和进化是至关重要的。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已经证明，这些突变基因和他研究系统中的突变基因来自同一一般遗传途径中的缺陷，进一步的研究表明，类似的种群水平的过程可能涉及实验室和自然界。因此，这个项目很可能在这些具有社会重要性的领域做出重大贡献。

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.