Rydén L G, Hunt L T
Department of Biochemistry, Uppsala University, Sweden.
J Mol Evol. 1993 Jan;36(1):41-66. doi: 10.1007/BF02407305.
The blue copper proteins and their relatives have been compared by sequence alignments, by comparison of three-dimensional structures, and by construction of phylogenetic trees. The group contains proteins varying in size from 100 residues to over 2,300 residues in a single chain, containing from zero to nine copper atoms, and with a broad variation in function ranging from electron carrier proteins and oxidases to the blood coagulation factors V and VIII. Difference matrices show the sequence difference to be over 90% for many pairs in the group, yet alignment scores and other evidence suggest that they all evolved from a common ancestor. We have attempted to delineate how this evolution took place and in particular to define the mechanisms by which these proteins acquired an ever-increasing complexity in structure and function. We find evidence for six such mechanisms in this group of proteins: domain enlargement, in which a single domain increases in size from about 100 residues up to 210; domain duplication, which allows for a size increase from about 170 to about 1,000 residues; segment elongation, in which a small segment undergoes multiple successive duplications that can increase the chain size 50-fold; domain recruitment, in which a domain coded elsewhere in the genome is added on to the peptide chain; subunit formation, to form multisubunit proteins; and glycosylation, which in some cases doubles the size of the protein molecule. Size increase allows for the evolution of new catalytic properties, in particular the oxidase function, and for the formation of coagulation factors with multiple interaction sites and regulatory properties. The blood coagulation system is examined as an example in which a system of interacting proteins evolved by successive duplications of larger parts of the genome. The evolution of size, functionality, and diversity is compared with the general question of increase in size and complexity in biology.
通过序列比对、三维结构比较以及系统发育树构建，对蓝色铜蛋白及其相关蛋白进行了比较。该蛋白家族包含单链大小从100个残基到超过2300个残基不等的蛋白质，含铜原子数从零到九个，功能广泛多样，从电子载体蛋白、氧化酶到凝血因子V和VIII。差异矩阵显示，该家族中许多蛋白对的序列差异超过90%，但比对得分和其他证据表明它们都起源于一个共同祖先。我们试图描绘这种进化是如何发生的，特别是确定这些蛋白质在结构和功能上获得不断增加的复杂性的机制。我们在这组蛋白质中发现了六种这样的机制：结构域扩大，即单个结构域大小从约100个残基增加到210个；结构域重复，可使大小从约170个残基增加到约1000个；片段延伸，即一小段经历多次连续重复，可使链大小增加50倍；结构域招募，即基因组其他地方编码的结构域添加到肽链上；亚基形成，形成多亚基蛋白质；以及糖基化，在某些情况下可使蛋白质分子大小翻倍。大小增加允许新催化特性的进化，特别是氧化酶功能，以及形成具有多个相互作用位点和调节特性的凝血因子。以凝血系统为例进行研究，其中相互作用的蛋白质系统通过基因组较大部分的连续重复而进化。将大小、功能和多样性的进化与生物学中大小和复杂性增加的一般问题进行了比较。
