Synthetic Gene Recruitment Reveals Adaptive Reprogramming of Gene Regulation in Yeast

Open Access
Publisher Website
Google Scholar
Abstract
The recruitment of a gene to a foreign regulatory system is a major evolutionary event that can lead to novel phenotypes. However, the evolvability potential of cells depends on their ability to cope with challenges presented by gene recruitment. To study this ability, we combined synthetic gene recruitment with continuous culture and online measurements of the metabolic and regulatory dynamics over long timescales. The gene HIS3 from the histidine synthesis pathway was recruited to the GAL system, responsible for galactose utilization in the yeast S. cerevisiae. Following a switch from galactose to glucose—from induced to repressed conditions of the GAL system—in histidine-lacking chemostats (where the recruited HIS3 is essential), the regulatory system reprogrammed to adaptively tune HIS3 expression, allowing the cells to grow competitively in pure glucose. The adapted state was maintained for hundreds of generations in various environments. The timescales involved and the reproducibility of separate experiments render spontaneous mutations an unlikely underlying mechanism. Essentially all cells could adapt, excluding selection over a genetically variable population. The results reveal heritable adaptation induced by the exposure to glucose. They demonstrate that genetic regulatory networks have the potential to support highly demanding events of gene recruitment.