Tracking buffers of mutation and noise to the genome

Abstract

Phenotypes are buffered from both genetic perturbations and developmental noise; however, the mechanisms by which this buffering occurs and its evolutionary relevance are poorly understood. In this dissertation, a combination of genetic and computational approaches were undertaken to not only identify genetic loci that are buffered from phenotypes but also map genes that provide phenotypic buffering. For example, I found that substrates of Heat shock protein 90 (Hsp90), the best-understood source of buffering, tend to accumulate genetic changes in a manner that affects evolution. Hsp90 is also a proven buffer of developmental noise, so the mechanism by which this ability arises was explored. To expand the number of known developmental noise buffers, innovative methods for genome-wide association were used to map novel regulators. The ability to identify loci that are buffered and provide buffering indicates that the distribution of phenotypes across a population arises through complex interactions between genetic loci, including genes that act as buffers.