Research

Mutation is the source of all genetic variation, producing both positive consequences, such as adaptation, and negative consequences, including genetic disorders. Despite its importance, we still have a lot to learn about mutation. Why does the rate of mutation vary among species, genotypes, and genome architectures? How do the rate and fitness consequences of mutations vary across environments?What makes some sites in a genome more susceptible to mutation than others? What drives the evolution of the mutation process itself? Work in our lab incorporates not just single-nucleotide changes, but also the wide spectrum of structural alterations that can dramatically alter genetic structure, promote adaptation, or lead to disease. Using experiments with yeast and fruit flies, combined with genome sequencing and bioinformatics, the Sharp Lab examines these and other aspects of mutation to broaden our understanding of this fundamental genetic process.

Publications

• Sharp NP, Sandell L, James CG, Otto SP. (2018) The genome-wide rate and spectrum of spontaneous mutations differ between haploid and diploid yeast. Proceedings of the National Academy of Sciences USA 115: E5046-5055.
• Sharp NP, Agrawal AF. (2018) An experimental test of the mutation-selection balance model for the maintenance of genetic variance in fitness components. Proceedings of the Royal Society B 285: 20181864.
• Sharp NP, Otto SP (2016) Evolution of sex: Using experimental genomics to select among competing theories. BioEssays 38: 751-757. Sharp NP, Agrawal AF (2016) Low genetic quality affects key dimensions of the mutational spectrum. PLoS Biology 14: e1002419.
• Sharp NP, Agrawal AF (2013) Male-biased fitness effects of spontaneous mutations in Drosophila melanogaster. Evolution 67: 1189-1195. Sharp NP, Agrawal AF (2012) Evidence for elevated mutation rates in low-quality genotypes. Proceedings of the National Academy of Sciences USA 109:6142-6146.