Epistasis, Pleiotropy, and Evolutionary Dynamics

Abstract

The advent of technologies for expedient nucleic acid sequencing, synthesis, assembly, and editing has opened up new vistas for exploring the genetic causes and consequences of evolutionary dynamics. In particular, it has facilitated the exploration of the empirical map relating genotype to phenotype. Through a combination of experimental evolution and genetic engineering, researchers can study how this map interacts with evolutionary processes to produce adaptive outcomes, particularly in microbial populations.

In this thesis, I describe work in which my colleagues and I have used experimental populations of budding yeast to better understand two features of fitness landscapes important to shaping adaptive trajectories: epistasis and pleiotropy. In Chapter 2, I describe the construction of a large multigene fitness landscape, which allowed us to demonstrate that just a few idiosyncratic interactions can readily give rise to prevalent trends of diminishing returns and increasing costs with respect to the effects of beneficial and deleterious mutations, respectively. In Chapter 3, I recount work in which we uncovered the genetic basis of the differential propensity of laboratory yeast strains and natural isolates to commonly fix spontaneous whole-genome duplications during haploid experimental evolution, an event that causes a drastic shift in the evolutionary dynamics of these populations. And in Chapter 4, I describe research that provides a window onto the emergence of pleiotropic effects over the course of 1000 generations of diploid and haploid yeast evolution, revealing predictable but variable adaptive trajectories across replicate populations that are specific to different evolution conditions. Finally, in Chapter 5, I review our findings and speculate on promising future directions for this research.