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Start of funding 01.01.2015

Molecular mechanisms of evolution of gene regulatory circuits

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The ability to control gene expression is essential for most cells to function properly. At its core, this control is provided by sequence-specific DNA binding proteins. We, as well as other groups, have shown that small changes in the binding specificities of these proteins over evolutionary timescales can drive the emergence of new traits in many organisms. This finding raises fundamental questions about the mechanism(s) that make(s) this possible: What type of modifications can these proteins undergo and how do these changes impinge upon the regulatory circuitry of an organism? In collaboration with Dr. Fordyce s group at Stanford University, we will determine the full profile of DNA sequences that a family of yeast transcription factor proteins can recognize along with their specificity and binding affinity. This information will allow us to infer a logical series of steps that led to the divergence of this family of proteins and the novel functions that they acquired.

Final report:
The main goal of the BaCaTeC-funded project between Würzburg (Dr. Pérez lab) and Stanford (Dr. Fordyce lab) was to bring together complementary expertise to investigate how evolutionary changes in sequence-specific DNA binding proteins drive the emergence of biological novelty. As a case study, we focused on characterizing a family of yeast proteins that appear to have been key in enabling some fungi to inhabit the human body. At Stanford, we employed a microfluidics-based approach developed by Dr. Fordyce to systematically measure the DNA sequence preferences of the proteins. Dr. Pérez and one of his doctoral students traveled to Stanford on separate occasions to conduct these experiments and learn more about this technique. Back in Würzburg, we have conducted more targeted DNA-protein measurements, as well as in vivo assays, to validate and expand on the data gathered at Stanford. Results of this project were presented in the International EMBO Conference “Experimental Approaches to Evolution and Ecology using Yeast and Other Model Systems” held in Heidelberg in October 2016. A joint scientific manuscript based on this project is currently being drafted and we expect to submit it for publication in the following months.