Lineage-Specific Duplication and Loss of Pepsinogen Genes in Hominoid Evolution
Lineage-Specific Duplication and Loss of Pepsinogen Genes in Hominoid Evolution
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DOI：
10.1007/s00239-010-9320-8
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发表时间：
2010-04-01
影响因子：
3.9
通讯作者：
Kageyama, Takashi
中科院分区：
文献类型：
--
作者：
Narita, Yuichi;Oda, Sen-ichi;Kageyama, Takashi
从猩猩Pongo pygmaeus的胃粘膜中克隆了14种不同的胃蛋白酶原-A cDNA和1种胃蛋白酶原-C cDNA。编码的胃蛋白酶原A分为两组，即，A1型和A2型，酸性不同。A1和A2基因分别有9个和5个等位基因（至少5个和3个位点）。黑猩猩基因组中存在相应的正向同源基因，尽管它们的拷贝数比猩猩基因的拷贝数小得多。只有A1基因存在于人类中，可能是由于A2基因的丢失。分子系统发育分析表明，A1和A2基因分歧之前的物种形成的大型人科动物。在猩猩谱系中，相应基因的进一步重复发生了几次，频率远远高于黑猩猩和人类谱系。在A2基因谱系中，非同义替换的发生率高于同义替换，说明正选择对A2基因编码的酶有一定的作用。胃蛋白酶的几个位点确实被发现处于正选择作用下，其中大多数位于分子表面，参与构象柔性。从已知的灵长类和其他哺乳动物胃蛋白酶原-A基因的基因组结构推断，在它们的进化过程中，重复/丢失是频繁的。由于胃内酶水平的增加和酶特异性的多样化，猩猩的极端繁殖可能有利于对草本食物的消化。
Fourteen different pepsinogen-A cDNAs and one pepsinogen-C cDNA have been cloned from gastric mucosa of the orangutan, Pongo pygmaeus. Encoded pepsinogens A were classified into two groups, i.e., types A1 and A2, which are different in acidic character. The occurrence of 9 and 5 alleles of A1 and A2 genes (at least 5 and 3 loci), respectively was anticipated. Respective orthologous genes are present in the chimpanzee genome although their copy numbers are much smaller than those of the orangutan genes. Only A1 genes are present in the human probably due to the loss of the A2 gene. Molecular phylogenetic analyses showed that A1 and A2 genes diverged before the speciation of great hominoids. Further reduplications of respective genes occurred several times in the orangutan lineage, with much higher frequencies than those occurred in the chimpanzee and human lineages. The rates of non-synonymous substitutions were higher than those of synonymous ones in the lineage of A2 genes, implying the contribution of the positive selection on the encoded enzymes. Several sites of pepsin moieties were indeed found to be under positive selection, and most of them locate on the surface of the molecule, being involved in the conformational flexibility. Deduced from the known genomic structures of pepsinogen-A genes of primates and other mammals, the duplication/loss were frequent during their evolution. The extreme multiplication in the orangutan might be advantageous for digestion of herbaceous foods due to the increase in the level of enzymes in stomach and the diversification of enzyme specificity.