Dynamics of Mutator Evolution: An Experimental Study

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

9981518 Sniegowski This project will study why high rates of genetic mutation arise and persist in bacterial populations. The PI has previously documented the origin and persistence of high mutation rates caused by mutator genes in populations of Escherichia coli that have been propagated in the laboratory. The three goals of the current project are: 1) to understand why mutator genes are successful; 2) to study the dynamics of mutator genes in populations; and 3) to document the DNA sequence changes that give rise to mutator genes in these populations. Goals 1 and 2 will be achieved through laboratory experiments in which E. coli cells bearing mutator genes are competed against their normal counterparts. Goal 3 will be achieved by DNA sequencing of mutator genes. Because mutation is the ultimate source of genetic variation, elucidating how mutation rates are established and maintained is of fundamental importance to our understanding of genetics and evolution. But substantial societal implications exist as well: Mutator genes have been associated with pathogenicity in bacteria and with cancer in humans. The PI has shown that these mutator genes and the mutators in his study system arise from defects in the same general genetic pathway, and further research has suggested that similar population-level processes are likely to be involved in the laboratory and in nature. This project is therefore likely to contribute significant insights in these areas of societal importance.