Biophysical models of evolution

The recent emergence of quantitative high-throughput experimental technology and new biophysical knowledge may finally enable significant empirical and quantitative understanding of adaptive evolution, which has been elusive for almost a century. The modern aim is to unite classical population genetics with biophysical molecular models, and to connect physical properties of biological molecules such as DNA, RNA and proteins with evolutionary parameters. In this vein, I have studied such population models theoretically, and applied one such model to yeast evolution. In Chapters 2 and 3, I will discuss “universality” in population genetics, in particular the universal applicability of a formula for the steady state distribution of phenotypes in a population evolving in the “monomorphic regime”, which describes most organisms. I show that this formula applies far outside the “weak selection” context it was originally developed in, and that it is a universal feature of evolution in this regime. Such universal features will be important components of any grand theory of adaptive evolution, and are essential for studies of real populations where the microscopic population dynamics are generally unknown. I then apply this model to a particular molecular system in yeast, Transcription Factor binding sites, which are short DNA sequences which play an important role in iigene regulation. Using the functional relationship between evolutionary fitness and the phenotypic steady state distribution, I infer the form of the selective pressure the sites experience, and find it is consistent with a simple thermodynamic model of two-state TF-DNA binding. I also show that the selection pressure a site experiences is decoupled from the selection pressure on the gene it regulates. This suggests that binding sites for a given TF evolve over a universal fitness landscape derived from simple physical interactions.Ph. D.Includes bibliographical referencesby Allan M. Haldan