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、生物能量代谢、催化反应以及作为药物靶点等方面发挥关键作用。本研究发现，膜蛋白的可检测直系同源物（ortholog）数量显著少于水溶性蛋白（water-soluble proteins），在多数分析物种中仅为水溶性蛋白的一半以下。这种稀疏的分布特征可能源于快速分化或基因丢失，本研究证实这两种机制均存在：其一，膜蛋白的进化速率快于水溶性蛋白，尤其是其膜外侧暴露结构域；其二，在亲缘关系较近的古菌（archaea）与细菌（bacteria）物种中，预测得到的祖先膜蛋白相较于水溶性蛋白更易发生丢失。 上述规律在整个生命之树以及古菌、细菌、真核生物（eukaryotes）这三大生物域中均成立。本研究结果揭示了一项基础进化规律：膜蛋白因在多变环境中受到更强的适应性选择而进化更快，而胞质蛋白则在细胞稳态的内部环境中承受更为严格的纯化选择。该效应在原核生物（prokaryotes）中最为显著，在具有内膜系统的单细胞真核生物中次之，而在具备胞外稳态机制的多细胞真核生物中最弱，本研究证实了这一结论。类似地，本研究发现胞外水溶性蛋白相较于膜蛋白，其同源性偏低的特征更为显著。膜蛋白与水溶性蛋白在保守性上的这些显著差异，对进化生物学与医学研究均具有重要意义。