PgmNr P2059: Evolution of gene regulation in nutrient starvation response between free-living and commensal yeast.

Authors:
Bin He; Xu Zhou; Erin O'Shea


Institutes
Harvard University, Cambridge, MA.


Abstract:

The genomic processes behind local adaptation can be revealed by applying functional genomics in a comparative framework. Here I present work on the evolution of phosphate starvation response bewteen the model organism, S. cerevisiae, and a close relative, Candida glabrata. C. glabrata is a post-genome-duplication species, same as S. cerevisiae. Yet since their divergence, it has acquired abilities to colonize mammal gut. Preliminary studies of its phosphate starvation response revealed a puzzling difference in the regulation of the pathway. While the master transcription factor PHO4 in S. cerevisiae requires a co-factor (PHO2) to function, this dependence is lost in C. glabrata. Interestingly, the ortholog of the PHO2 in C. glabrata still functions and binds adjacent to most of the Pho4 sites, yet its Pho4 is able to bind and activate gene expression independent of Pho2. Using transcriptome profiling and chromatin IP, we mapped genome-wide binding sites of both PHO4 and their co-factor in each species’ genome, and identified PHO4 dependent genes, respectively. We found that (1) loss of dependence on the co-factor results in expansion of PHO4’s targets. (2) accompanying cis co-evolution modulates the extent of target expansion in C. glabrata. (3) functional annotation of PHO4 targets in C. glabrata suggests cross-activation of genes involved in other stress responses. Remarkably, a survey of PHO4 orthologs in divergent yeast species revealed two independent events for loss of PHO2-dependence, both in commensal species, suggesting the change is likely beneficial in that context.