Naoi Y, Chong K T, Yoshimatsu K, Miyazaki G, Tame J R, Park S Y, Adachi S, Morimoto H
Division of Biophysical Engineering, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
J Mol Biol. 2001 Mar 16;307(1):259-70. doi: 10.1006/jmbi.2000.4446.
Although many descriptions of adaptive molecular evolution of vertebrate hemoglobins (Hb) can be found in physiological text books, they are based mainly on changes of the primary structure and place more emphasis on conservation than alterations at the functional site. Sequence analysis alone, however, does not reveal much about the evolution of new functions in proteins. It was found recently that there are many functionally important structural differences between human and a ray (Dasyatis akajei) Hb even where sequence is conserved between the two. We have solved the structures of the deoxy and CO forms of a second cartilaginous fish (a shark, Mustelus griseus) Hb, and compared it with structures of human Hb, two bony fish Hbs and the ray Hb in order to understand more about how vertebrate Hbs have functionally evolved by the selection of random amino acid substitutions. The sequence identity of cartilaginous fish Hb and human Hb is a little less than 40 %, with many functionally important amino acid replacements. Wider substitutions than usually considered as neutral have been accepted in the course of molecular evolution of Hb. As with the ray Hb, the shark Hb shows functionally important structural differences from human Hb that involve amino acid substitutions and shifts of preserved amino acid residues induced by substitutions in other parts of the molecule. Most importantly, beta E11Val in deoxy human Hb, which overlaps the ligand binding site and is considered to play a key role in controlling the oxygen affinity, moves away about 1 A in both the shark and ray Hbs. Thus adaptive molecular evolution is feasible as a result of both functionally significant mutations and deviations of preserved amino acid residues induced by other amino acid substitutions.
尽管在生理学教科书中可以找到许多关于脊椎动物血红蛋白（Hb）适应性分子进化的描述，但这些描述主要基于一级结构的变化，并且更强调保守性而非功能位点的改变。然而，仅靠序列分析并不能揭示蛋白质新功能的进化情况。最近发现，即使人类和赤魟（Dasyatis akajei）的血红蛋白在序列上保守，两者之间仍存在许多功能上重要的结构差异。我们解析了第二种软骨鱼类（一种鲨鱼，灰星鲨Mustelus griseus）血红蛋白的脱氧和一氧化碳结合形式的结构，并将其与人类血红蛋白、两种硬骨鱼类血红蛋白以及赤魟血红蛋白的结构进行比较，以便更深入地了解脊椎动物血红蛋白是如何通过随机氨基酸替换的选择在功能上进化的。软骨鱼类血红蛋白与人类血红蛋白的序列同一性略低于40%，存在许多功能上重要的氨基酸替换。在血红蛋白的分子进化过程中，比通常认为是中性的替换范围更广泛的替换也被接受了。与赤魟血红蛋白一样，鲨鱼血红蛋白与人类血红蛋白在功能上存在重要的结构差异，这些差异涉及氨基酸替换以及分子其他部分的替换所诱导的保守氨基酸残基的位移。最重要的是，在脱氧人类血红蛋白中与配体结合位点重叠且被认为在控制氧亲和力方面起关键作用的βE11Val，在鲨鱼和赤魟血红蛋白中都向外移动了约1埃。因此，由于功能上显著的突变以及其他氨基酸替换所诱导的保守氨基酸残基的位移，适应性分子进化是可行的。
