Variation in the environment in which genotypes are translated into phenotypes can both induce phenotypic differences through plasticity and filter phenotypic variation for different optima via natural selection. Understanding the evolution of plasticity thus requires disentangling the role of environment as an agent of development and as an agent of selection, possible only through studying the phenotypic effects of new mutations not yet subject to selection. Here I propose to investigate the effects of new mutations on gene expression levels across environmental contexts in budding yeast. Taking advantage of a high throughput screen for isolating new mutations influencing gene expression, I will characterize the distribution of mutational effects on gene expression and the degree of correlation among the effects of individual new mutations across environments for nine genes. Through site-directed mutagenesis, I will investigate the effects of cis regulatory mutations on gene expression to identify the breadth of expression changes possible across environments through disruption of known regulatory motifs, and measure their consequences for growth. By examining the effects of these new regulatory mutations on fitness, I will characterize the evolutionary signal for selection on plasticity in gene expression.
This project examines the properties of mutations that affect gene expression across multiple environments and how they relate to fitness, and has two major consequences for human health. The first is a better basic science understanding of the range of possible effects that the environment may have on the mapping from DNA variant to phenotypic effect. The second concerns the ability of a population of cells experiencing a novel environment to persist and evolve, which is particularly important for issues including cancer metastasis and the ability of pathogens to jump into new species.
| Duveau, Fabien; Hodgins-Davis, Andrea; Metzger, Brian Ph et al. (2018) Fitness effects of altering gene expression noise in Saccharomyces cerevisiae. Elife 7: |
| Duveau, Fabien; Yuan, David C; Metzger, Brian P H et al. (2017) Effects of mutation and selection on plasticity of a promoter activity in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 114:E11218-E11227 |
