Title: Quantitative insights into gene network evolution and aging in the context of a canonical network
Regulation of gene expression in the yeast galactose utilization network has served as a paradigm for eukaryotic transcriptional control for 60 years now. Using the GAL network as an experimental model, we characterized cross-species evolution of this network and how cellular aging affected the network activity. Combinatorial replacement of the network promoters in S. cerevisiae by their counterparts from the yeast S. paradoxus provided insights into the role of a key cis-regulatory region as a facilitator of network evolution between the two yeast species. Tracking the activity of the GAL network in budding yeast cells monitored throughout their replicative lifespan in a microfluidic chamber elucidated how gene expression levels and noise in gene expression dynamically change during the aging of the host cell. Aging-associated increases in chromatin state transitions were hypothesized to be behind the observed gene expression and noise dynamics, and a stochastic model provided quantitative support to the proposed mechanism. Future studies on other model organisms and/or gene networks will show the degree of generality of our results.
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