CBE/ENGR 225 Faculty Seminar: Dawn Thompson, Ph.D., Senior Biological Engineer at Ginkgo Bioworks, Inc., Broad Institute
Dawn Thompson, Ph.D.
Senior Biological Engineer at Ginkgo Bioworks, Inc., Broad Institute
Tuesday, March 1, 2016
*Light refreshments will be provided*
Duplication of a Conserved Transcriptional Regulator
Drives Evolutionary Novelty in Yeasts
Divergence in gene regulation can play a major role in evolution. We developed a phylogenetic framework to measure mRNA profiles in 15 yeast species and reconstruct the evolution of their modular regulatory programs. We found that modules diverge with phylogenetic distance, with prominent regulatory changes accompanying changes in carbon lifestyle and ploidy. Gene paralogs have significantly contributed this regulatory divergence. To explore the role of trans regulator duplication, we focused on the transcription factor (TF) Sfp1 since gain or loss of the Sfp1 binding site underlied regulatory rewiring of carbon metabolism. In S. cerevisiae Sfp1, a TOR target, activates transcription of “growth” genes, e.g. ribosome biogenesis. S. cerevisiae, sfp1∆ mutants have smaller cells and slower growth, suggesting that these two phenotypes are closely intertwined.However, we show that duplication of SFP1 in other yeast species has resulted in both sub- and neo-functionalization of the regulatory programs controlling growth rate and cell size. To better understand how the Sfp1-regulatory program has evolved to produce novel phenotypes, we used a two-tiered system of comparing gene expression and ChIP-Seq data to distinguish indirect or direct Sfp1 targets in a subset of species and then trace the evolution of targets (and their functions) across species.
At the end of the talk, I will discuss how we apply this framework in my new position as Senior Biological Engineer at Ginkgo Bioworks an organism engineering company.