UCSF

The mystery of how diverse life forms evolved has captivated scientists for over 150 years. It has become clear that many diverse life forms harbor similar sets of genes and that their diversity must arise from differences in the time and place those genes are deployed. Regulation and organization of these genes into networks is carried out by transcription factors and their cis-regulatory sites, but many questions remain about how they evolve. For example, the classical view of molecular biology is that genes and their molecular functions are precisely adapted to work for the organism. Instead, transcription networks—and genes themselves—are often “just good enough” to carry out their functions, because they are constrained by biochemistry and degraded by mutation and genetic drift.

To understand how organismal diversity evolved, it is necessary to understand the organismal function, the molecular architecture, and the evolutionary forces that affect each trait. The mating system in yeast is one example of a case in which these disparate pieces of information can be combined. A particular set of mating genes are part of two networks: the cell-type network and the pheromone-response network. They are expressed only in the a cell type (but not the alpha cell type), and when the yeast cell senses pheromone, their expression increases. I found that multiple successive changes in one network altered the evolution of the other network. If any of these changes happened out of order, the expression of the genes was disrupted, suggesting strong constrains in the evolutionary paths of these two networks.

A second major question is how the expression of large numbers of genes can evolve simultaneously. In the final chapter I propose that a molecular mechanism explains the rewiring of the ribosomal proteins in yeast by the transcription factor Mcm1. This gain occurred at least three times in a set of yeast that last had a common ancestor ~150 million years ago. The mechanism—cooperative recruitment—explains how two transcription factors can work together through interacting with a common downstream factor, facilitating the repeated evolution of their cis-regulatory sites in close proximity.