Data from: Membrane proteins are dramatically less conserved than water-soluble proteins across the tree of life

Membrane proteins are crucial in transport, signaling, bioenergetics, catalysis, and as drug targets. Here we show that membrane proteins have dramatically fewer detectable orthologs than water-soluble proteins, less than half in most species analyzed. This sparse distribution could reflect rapid divergence or gene loss. We find that both mechanisms operate. First, membrane proteins evolve faster than water-soluble proteins, particularly in their exteriorfacing portions. Second, we demonstrate that predicted ancestral membrane proteins are preferentially lost compared with water-soluble proteins in closely related species of archaea and bacteria. These patterns are consistent across the whole tree of life, and in each of the three domains of archaea, bacteria, and eukaryotes. Our findings point to a fundamental evolutionary principle: membrane proteins evolve faster due to stronger adaptive selection in changing environments, while cytosolic proteins are under more stringent purifying selection in the homeostatic interior of the cell. This effect should be strongest in prokaryotes, weaker in unicellular eukaryotes (with intracellular membranes), and weakest in multicellular eukaryotes (with extracellular homeostasis). We demonstrate that this is indeed the case. Similarly, we show that extracellular water-soluble proteins exhibit an even stronger pattern of low homology than membrane proteins. These striking differences in conservation of membrane proteins versus water-soluble proteins have important implications for evolution and medicine.膜蛋白（membrane proteins）在物质转运、信号传导、生物能代谢、催化反应中发挥关键功能，同时亦是重要的药物作用靶点。本研究发现，膜蛋白的可检测直系同源物（orthologs）数量远低于水溶性蛋白（water-soluble proteins），在多数分析物种中仅为水溶性蛋白的一半以下。这种稀缺的分布特征可能源于快速分化或基因丢失，本研究证实两种机制均参与其中。其一，膜蛋白的进化速率快于水溶性蛋白，尤其是在其胞外侧区段；其二，在亲缘关系较近的古菌（archaea）与细菌（bacteria）物种中，相较于水溶性蛋白，预测得到的祖先膜蛋白更易发生丢失。上述演化模式在整个生命之树以及古菌、细菌、真核生物（eukaryotes）三大生物类群中均保持一致。本研究结果揭示了一项基础演化原则：膜蛋白因在多变环境中承受更强的适应性选择压力而进化更快，而胞质蛋白（cytosolic proteins）则在细胞内稳态的胞内环境中受到更为严格的纯化选择。这一效应在原核生物（prokaryotes）中最为显著，在具有胞内膜结构的单细胞真核生物中强度次之，而在具备胞外稳态机制的多细胞真核生物中最弱，本研究证实这一推测与实际观测结果完全吻合。类似地，本研究发现胞外水溶性蛋白（extracellular water-soluble proteins）相较于膜蛋白，其序列同源性更低的特征更为显著。膜蛋白与水溶性蛋白在序列保守性上的显著差异，对演化生物学与医学研究均具有重要价值。