As one of eight finalists among hundreds of applicants, he presented a seminar at the plenary session of the summer SMBE conference in Chicago. His title is “Disentangling the effects of mutation and selection on the evolution of regulatory sequences.” The Fitch prize is the most prestigious student award given annually by SMBE. Metzger’s advisors are Professors Patricia Wittkopp and Jianzhi Zhang.
“In order for a gene to be useful, it must first be expressed,” explained Metzger. “Mutations that change where, when, or how much a gene is expressed are known to be common and play a large role in evolution. Unfortunately, our understanding of how the regulatory regions which control gene expression evolution is limited. In particular, our ability to detect natural selection acting in regulatory regions is very poor.”
“To solve this problem, we created over 250 mutants in the regulatory region of a single gene in the yeast Saccharomyces cerevisiae. These mutants were engineered to differ by only a single DNA base pair, allowing us to determine the effects on gene expression of each mutation individually. Because of how these mutants were made, they experienced no natural selection. This allowed us to see what the evolution of gene expression would look like if there was no natural selection.
“We then used a collection of S. cerevisiae strains isolated from all over the world and other Saccharomyces species to figure out which of these mutations actually happened in nature, the order in which they happened, and their effects on gene expression when they happened. We compared the effects that happened in nature to the effects we measured in our laboratory mutants and found that they were different, but not in the way we expected. We found that there was no difference in gene expression between the groups of mutants. Instead, we found that mutations in the wild resulted in lower expression noise, i.e. variability in expression between individuals. For this gene, it appears that what selection actually cares about is keeping variation in expression low, not so much the actual level of expression. Thus, this research highlights not only a method for detecting natural selection in regulatory regions, but also the importance of variability in expression to evolution.”
Beginning with the first annual meeting of the SMBE in 1993, the Walter M. Fitch Symposium has provided a forum for young investigators to showcase their exemplary research. The Fitch Award honors the best presentation at this symposium.
Fitch was a pioneer in many areas of molecular evolution, in particular the methodology of phylogenetic reconstruction, the estimation of genetic distances, the study of rate constancy in proteins and DNA sequences, the evolution of codon usage, and retroviral evolution. He also made significant contributions to virology, the origin of life, taxonomy, genetics, and molecular biology.