Reverse Evolution of a Classic Gene Network in Yeast Offers a Competitive Advantage
Reverse Evolution of a Classic Gene Network in Yeast Offers a Competitive Advantage
复制标题
酵母中经典基因网络的逆向进化提供了竞争优势
DOI：
10.1016/j.cub.2019.02.038
复制
发表时间：
2019-04-01
期刊：
影响因子：
9.2
通讯作者：
Bai, Feng-Yan
中科院分区：
文献类型：
--
作者：
Duan, Shou-Fu;Shi, Jun-Yan;Bai, Feng-Yan
葡萄糖抑制是酵母中的一个中央调节系统，可确保以高度经济的方式利用碳源。半乳糖（GAL）代谢网络受到酵母中葡萄糖抑制的严格调控，并且一直是研究基因调控的经典系统。我们在此表明，自发发酵乳中的酿酒酵母 (S. cerevisiae) 谱系已通过基因渗入将其所有结构 GAL 基因（GAL2 和 GAL7-10-1 簇）替换为早期分化的版本。重新连接的 GAL 网络废除了葡萄糖抑制，并通过网络调节组件的多基因变化从严格诱导的系统转变为组成型系统，包括分别在 GAL1 和 GAL4 的上游抑制序列 (URS) 位点中胸腺嘧啶 (T) 到胞嘧啶 (C) 和鸟嘌呤 (G) 到腺嘌呤 (A) 的转变，这损害了 Mig1p 介导的抑制，使 GAL 网络功能丧失。通过蛋白质中的 T1461 取代来抑制 Gal80p，随后 GALS 无效。此外，酿酒酵母的乳谱系通过基因渗入的GAL2的复制和主要葡萄糖转运蛋白基因HXT6和HXT7的功能丧失，实现了半乳糖利用率的提高和半乳糖相对于葡萄糖的偏好转换。此外，我们证明，GAL2 需要 GAL7 或 GAL10 才能表达，而 Gal2p 可能需要 Gall p 才能在酿酒酵母乳谱系中发挥运输功能。我们展示了一个用于生态适应的经典基因网络逆向进化的清晰案例，并为规范 GAL 网络的调控模型提供了新的见解。
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 T1461 substitution in the protein, and subsequent futility of GALS. 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 Gall p 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.