We are broadly interested in the genetic basis of evolutionary change and specifically interested in the role of changes in gene regulation. We combine analysis of gene expression with population genetic and molecular evolution models to understand when changes in cis-regulatory sequences matter. In yeast we study diversification of Saccharomyces species and differentiation of wild and domesticated strains of S. cerevisiae used for beer, bread and wine production. In humans we study the genetic basis of preterm birth. Our goal is to understand how these systems evolved. Current projects include:
Most cis-regulatory sequences are defined by expression levels (on/off) or expression patterns (e.g. developmental stage). However, cis-regulatory sequences may also control transcriptional dynamics, for example how long it takes to activate a gene. We are currently investigating mutations that alter transcriptional dynamics and their phenotypic consequences using allele-specific expression and fitness assays.
Domestication and diversification of yeast
Yeast has evolved the amazing ability to ferment sugar in the presence of oxygen, providing us with beer, bread and wine. While this fermentative lifestyle is not unique to S. cerevisiae, S. cerevisiae is the predominate species used for the production of fermented foods and beverages. One characteristic unique to S. cerevisiae is that it consistently outcompetes other microbes during wine fermentations. We are interested in which genes and what genetic changes lead to S. cerevisiae's unique characteristics and its widespread use for fermentation.
Despite the importance of delivering at the right time, we still do not understand what causes women to go into labor. In mice, labor is induced by loss of the hormone progesterone. However in humans progesterone levels remain high at the onset of labor. One reason why progesterone signaling and the initiation of labor may have changed during human evolution is to accommodate cephalopelvic constraints imposed by changes in brain size and the pelvis. In addition to morphological changes, the vaginal microbiome substantially differs between humans and other primates and has been associated with preterm birth. We are working on collaborative projects to identify genetic factors that cause women to go into labor and elucidate the role of vaginal microbial communities in preterm birth.
- Bergen AC, Olsen GM, Fay JC. 2016. Divergent MLS1 promoters lie on a fitness plateau for gene expression. Mol Biol Evol33:1270-9.
- Ludlow CL, Cromie GA, Garmendia-Torres C, Sirr A, Hays M, Field C, Jeffery EW, Fay JC, Dudley AM. 2016. Independent Origins of Yeast Associated with Coffee and Cacao Fermentation. Curr Biol26:965-71.
- Williams KM, Liu P, Fay JC. 2015. Evolution of ecological dominance of yeast species in high-sugar environments. Evolution69:2079-93.
- Hyma KE, Saerens SM, Verstrepen KJ, Fay JC. 2011. Divergence in wine characteristics produced by wild and domesticated strains of Saccharmoyces cerevisiae. FEMS Yeast Res11:540-51.
- Chun S, Fay JC. 2011. Evidence for hitchhiking of deleterious mutations within the human genome. PLoS Genet7:e1002240.
- Chun S, Fay JC. 2009. Identification of deleterious mutations within three human genomes. Genome Res19:1553-1561.
- Doniger SW, Fay JC. 2007. Frequency gain and loss of functional transcription factor binding sites. PloS Comput Biol3:e99.
- Fay JC, Benavides JA. 2005. Evidence for domesticated and wild populations of Saccharomyces cerevisiae. PLoS Genetics1:66-71.