Evolution of murine alpha 1-proteinase inhibitors: gene amplification and reactive center divergence.
Evolution of murine alpha 1-proteinase inhibitors: gene amplification and reactive center divergence.
复制标题
鼠α1-蛋白酶抑制剂的进化：基因扩增和反应中心分歧。
DOI：
10.1007/bf00166159
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发表时间：
1994
影响因子：
3.9
通讯作者：
Berger,FG
中科院分区：
文献类型：
--
作者：
Rheaume,C;Goodwin,RL;Latimer,JJ;Baumann,H;Berger,FG
α1蛋白酶抑制剂（α1PI）是哺乳动物血液中主要的丝氨酸蛋白酶抑制剂，其编码基因的组织和序列已在几种物种中进行了比较，包括小鼠啮齿类（genusMus）。基因拷贝数分析表明，α1PI基因的扩增发生在musgenus进化过程中的某个时间，导致在几个现有物种（如m.s homusand m.s homusand .）中固定了大约3至5个基因。而在其他物种中只有一个基因(如M。结论)。基于编码区域内的同义替换，构建了各种哺乳动物α1PI mrna的系统发育。在musgenus的第一个物种谱系形成之前，即大约1000万至1300万年前，不同鼠种的mrna从一个共同的祖先分化而来。因此，α1PI基因扩增一定发生在物种形成之前；基因家族保留在一些，但不是所有的老鼠物种中。α1PI多肽的反应中心区域决定了目标蛋白酶的特异性，在musspecies的进化过程中，α1PI多肽的反应中心区域迅速分化，但在分析中包括的其他哺乳动物物种的进化过程中没有分化。很可能这种加速进化的反应中心，已经注意到丝氨酸蛋白酶抑制剂，是由某种积极的达尔文选择驱动的，这种选择以一种特定的分类方式施加。我们认为，小鼠α1PI基因的进化具有基因拷贝数修饰和快速反应性中心分化的双重特征。这些过程可能导致蛋白酶抑制剂的范围扩大，这在进化过程中是有利的。
The organization and sequence of genes encoding the α1-proteinase inhibitor (α1PI), a major serine proteinase inhibitor of the mammalian bloodstream, have been compared in several species, including murine rodents (genusMus). Analysis of gene copy number indicates that amplification of α1PI genes occurred at some time during evolution of theMusgenus, leading to fixation of a family of about three to five genes in several existing species (e.g., M.domesticusandM. saxicola), and only a single gene in others (e.g.,M. caroli). A phylogeny for the various mammalian α1PI mRNAs was constructed based upon synonymous substitutions within coding regions. The mRNAs in different murine species diverged from a common ancestor before the formation of the first species lineages of theMusgenus, i.e., about 10–13 million years ago. Thus, α1PI gene amplification must have occurred prior toMusspeciation; gene families were retained in some, but not all, murine species. The reactive center region of the α1PI polypeptide, which determines target protease specificity, has diverged rapidly during evolution of theMusspecies, but not during evolution of other mammalian species included in the analysis. It is likely that this accelerated evolution of the reactive center, which has been noted previously for serine proteinase inhibitors, was driven by some sort of a positive Darwinian selection that was exerted in a taxon-specific manner. We suggest that evolution of α1PI genes of murine rodents has been characterized by both modification of gene copy number and rapid reactive center divergence. These processes may have resulted in a broadened repertoire of proteinase inhibitors that was evolutionarily advantageous duringMusspeciation.