Interdisciplinary Initiatives Program Round 6 - 2012

Daniel Fisher, Applied Physics
Gavin Sherlock, Genetics

Evolution is driven by new beneficial mutations. Yet as these mutations arise in individual organisms, their appearance and the initial dynamics of the mutant populations are hidden in the much larger numbers of their relatives -- most of whose descendants they will eventually drive to extinction. By the time a new beneficial mutation becomes abundant, it is masked by many other mutations and information about the identity and origins of even key mutations is usually lost. This project will analyze to an unprecedented depth the roots of beneficial mutations and follow the evolutionary processes as they occur. This will be done by focusing on laboratory evolution of yeast and using high-throughput DNA sequencing to track the descendants of hundreds of thousands of otherwise identical individuals that each have a unique DNA barcode. Combining this novel system with new mathematical analyses of the mutation and selection processes that occur in tiny subpopulations will enable extraction of some of the essential quantities that determine the evolutionary dynamics, in particular, the numbers and distribution of selective advantages of the beneficial mutations that arise.