Molecular Evolution in Large Populations

Abstract

In recent years, sequencing technologies have made it possible to observe molecular evolution in unprecedented detail. We now have detailed inventories of the present genetic variation in higher organisms and real-time tracking of mutations arising in rapidly adapting microbes and viruses. These populations often carry multiple closely linked selected mutations, making their fates interdependent, and posing new theoretical challenges that cannot be addressed by classical evolutionary theory. In this thesis, we study simple models of molecular evolution in large populations, with the aim of understanding how these complications to the classical picture may affect our interpretations of patterns of genetic diversity and our expectations for the predictability of molecular evolution. In Chapter 2, we review how careful observations of the dynamics of microbial adaptation in the laboratory have challenged previously held views and inspired new theoretical frameworks. In Chapter 3, we analyze a simple null model of molecular evolution in a "well-adapted" population in which selection acts only to maintain previously evolved traits. We find that even in this simple case, the dynamics of individual mutations can be remarkably complex, sometimes mimicking other evolutionary processes. In Chapter 4, we present a new high resolution method to observe laboratory microbial evolution at over long periods of time. We uncover a complex picture of rapid adaptation in which a combination of luck and merit shapes the fate of each mutation. Finally, in Chapter 5, we study the effect of environmental variation by modeling the dynamics of mutations that arise in a fluctuating environment.