Reverse Evolution of a Classic Gene Network in Yeast Offers a Competitive Advantage

• Published in: Current biology 2019-04, Vol.29 (7), p.1126-1136.e5
• Main Authors: Duan, Shou-Fu, Shi, Jun-Yan, Yin, Qi, Zhang, Ri-Peng, Han, Pei-Jie, Wang, Qi-Ming, Bai, Feng-Yan
• Format: Article
• Language: English
• Subjects: Base Sequence; ecological adaptation; Evolution, Molecular; GAL network; Gene Regulatory Networks - physiology; Genes, Fungal - genetics; Glucose - metabolism; glucose repression; introgression; reverse evolution; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - physiology; yeast
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2019.02.038

Glucose repression is a central regulatory system in yeast that ensures the utilization of carbon sources in a highly economical manner. The galactose (GAL) metabolism network is stringently regulated by glucose repression in yeast and has been a classic system for studying gene regulation. We show here that a Saccharomyces cerevisiae (S. cerevisiae) lineage in spontaneously fermented milk has swapped all its structural GAL genes (GAL2 and the GAL7-10-1 cluster) with early diverged versions through introgression. The rewired GAL network has abolished glucose repression and conversed from a strictly inducible to a constitutive system through polygenic changes in the regulatory components of the network, including a thymine (T) to cytosine (C) and a guanine (G) to adenine (A) transition in the upstream repressing sequence (URS) sites of GAL1 and GAL4, respectively, which impair Mig1p-mediated repression, loss of function of the repressor Gal80p through a T146I substitution in the protein, and subsequent futility of GAL3. Furthermore, the milk lineage of S. cerevisiae has achieved galactose-utilization rate elevation and galactose-over-glucose preference switch through the duplication of the introgressed GAL2 and the loss of function of the main glucose transporter genes HXT6 and HXT7. In addition, we demonstrate that GAL2 requires GAL7 or GAL10 for its expression, and Gal2p likely requires Gal1p for its transportation function in the milk lineage of S. cerevisiae. We show a clear case of reverse evolution of a classic gene network for ecological adaptation and provide new insights into the regulatory model of the canonical GAL network. [Display omitted] •A milk-adapted yeast lineage harbors early diverged versions of the structural GAL genes•The rewired GAL network is constitutively expressed and abolishes glucose repression•The adapted lineage prefers galactose to glucose, but it can co-utilize both sugars•GAL2 requires GAL7 or GAL10 for its expression and GAL1 for its function Duan et al. show that a milk-adapted yeast lineage harbors early diverged versions of the structural GAL genes. The rewired GAL network expresses constitutively and abolishes glucose repression. The adapted lineage prefers galactose to glucose, but it can co-utilize both sugars. GAL2 requires GAL7 or GAL10 for its expression and GAL1 for its function.