The structure of fitness landscapes across genotypes and environments

Abstract

Over the last 20 years, advances in experimental genetics have allowed us to map fitness landscapes at a scale and resolution that the likes of Fisher, Haldane, and Wright could not have even dreamed of a hundred years ago. These cutting-edge experimental methods have empowered us to try and understand the features of the evolutionary process in the wild by using experiments in the lab. In this dissertation, I will describe three such experimental projects that I undertook to map the fitness landscape across many different genotypes and environments in budding yeast. In chapter 2, I describe the process of molecular and phenotypic adaptation in the longest-running laboratory evolution experiment in budding yeast. In chapter 3, I report work in which we constructed, genotyped, and phenotyped ≈ 100,000 F1 offspring from a budding yeast cross and mapped the highly polygenic and epistatic fitness landscape in different environments at a resolution ≈ 10 times better than the previous state of the art. In chapter 4, I detail further experiments using the 100,000 F1 offspring where we measured their fitness in an extremely large panel of structured environments to understand the pleiotropic structure across environments and used it to map the functional organization of the cell. Finally, in chapter 5, I briefly summarize our results and mention promising future avenues for this body of work.