Molecular Mechanisms Underlying Yeast Transcription Circuit Evolution

/Abstract The rewiring of transcriptional circuits over evolutionary time is a major source of biological novelty. This proposal seeks to determine the detailed molecular mechanisms that underlie transcriptional rewiring using unicellular yeasts as a model system. The strategy is based on direct experimentation in many different yeast species in the Saccharomycetaceae lineage, and utilizes mutant construction, genome-wide transcriptional profiling, chromatin immunoprecipitation, phylogenetic comparisons, and ancestral protein reconstructions. Circuit comparisons among these yeasts will uncover specific examples of transcriptional rewiring, and deeper analyses will reveal the molecular mechanisms by which the wiring changes occurred. Although much rewiring is probably neutral, some of it appears adaptive: indeed, a major mechanism for evolutionary novelty involves rewiring transcriptional circuitry to allow new expression patterns of existing gene products. Thus, to truly understand the structures of transcription circuits in modern species, we need to know the mechanisms by which they rapidly evolve and how these mechanisms lead to and, thereby can account for, modern structures. Project Number: 1R35GM156460-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: ALEXANDER JOHNSON | Institution: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, SAN FRANCISCO, CA | Award Amount: $491,739 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award A Study Section[MRAA] View on NIH RePORTER: https://reporter.nih.gov/project-details/11010715