Gene Responses to Oxygen Availability in <em>Kluyveromyces lactis</em>: an Insight on the Evolution of the Oxygen-Responding System in Yeast

The whole-genome duplication (WGD) may provide a basis for the emergence of the very characteristic life style of Saccharomyces cerevisiae—its fermentation-oriented physiology and its capacity of growing in anaerobiosis. Indeed, we found an over-representation of oxygen-responding genes in the ohnologs of S. cerevisiae. Many of these duplicated genes are present as aerobic/hypoxic(anaerobic) pairs and form a specialized system responding to changing oxygen availability. HYP2/ANB1 and COX5A/COX5B are such gene pairs, and their unique orthologs in the ‘non-WGD’ Kluyveromyces lactis genome behaved like the aerobic versions of S. cerevisiae. ROX1 encodes a major oxygen-responding regulator in S. cerevisiae. The synteny, structural features and molecular function of putative KlROX1 were shown to be different from that of ROX1. The transition from the K. lactis-type ROX1 to the S. cerevisiae-type ROX1 could link up with the development of anaerobes in the yeast evolution. Bioinformatics and stochastic analyses of the Rox1p-binding site (YYYATTGTTCTC) in the upstream sequences of the S. cerevisiae Rox1p-mediated genes and of the K. lactis orthologs also indicated that K. lactis lacks the specific gene system responding to oxygen limiting environment, which is present in the ‘post-WGD’ genome of S. cerevisiae. These data suggested that the oxygen-responding system was born for the specialized physiology of S. cerevisiae.全基因组复制（whole-genome duplication, WGD）可为酿酒酵母（Saccharomyces cerevisiae）极具特征的生活方式——其以发酵为导向的生理特性以及厌氧生长能力——的起源提供基础。本研究团队在酿酒酵母的全基因组复制旁系同源基因（ohnologs）中发现了氧响应基因的显著富集。其中多数复制基因以有氧/低氧（厌氧）成对形式存在，构成了响应氧气浓度动态变化的特化调控系统。HYP2/ANB1与COX5A/COX5B便是这类基因对，它们在“非全基因组复制”（non-WGD）的乳酸克鲁维酵母（Kluyveromyces lactis）基因组中的唯一直系同源基因，其表达模式与酿酒酵母的有氧型同源基因一致。ROX1编码酿酒酵母中主要的氧响应调控因子。生物信息学分析显示，乳酸克鲁维酵母中推定的KlROX1基因的共线性、结构特征与分子功能均与ROX1存在显著差异。从乳酸克鲁维酵母型ROX1到酿酒酵母型ROX1的演化转变，或与酵母演化过程中厌氧适应性的形成紧密相关。对酿酒酵母ROX1p介导调控的基因及其乳酸克鲁维酵母同源基因上游序列中的Rox1p结合位点（YYYATTGTTCTC）开展生物信息学与随机分析后，结果同样表明：乳酸克鲁维酵母缺乏酿酒酵母“全基因组复制后”（post-WGD）基因组中所具备的、响应低氧环境的特化基因系统。上述研究结果提示，氧响应调控系统正是为适配酿酒酵母的特化生理特性而演化形成的。