Expansion of the mast cell chymase locus over the past 200 million years of mammalian evolution
Expansion of the mast cell chymase locus over the past 200 million years of mammalian evolution
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DOI：
10.1007/s00251-006-0126-1
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发表时间：
2006-08-01
期刊：
影响因子：
3.2
通讯作者：
Hellman, Lars
中科院分区：
文献类型：
--
作者：
Gallwitz, Maike;Reimer, Jenny M.;Hellman, Lars
自然杀伤 (NK) 细胞、T 细胞、肥大细胞和中性粒细胞的酸性颗粒储存大量丝氨酸蛋白酶。在功能上，这些蛋白酶参与细胞凋亡的诱导、炎症细胞的募集以及细胞外基质的重塑。颗粒蛋白酶包括系统发育相关的肥大细胞糜酶、中性粒细胞组织蛋白酶 G 和 T 细胞颗粒酶（Gzm B 至 H 和 Gzm N），它们都具有缺乏 Cys(191)-Cys(220) 桥的特征。在所有先前研究的哺乳动物中，这些蛋白酶的基因聚集在一个基因座，即肥大细胞食糜酶基因座。在本文中，我们对牛（Bos taurus）和负鼠（Monodelphis Domestica）的食糜酶基因座进行了详细分析。获得的信息描绘了两亿多年来食糜酶基因座的演变。令人惊讶的是，牛食糜酶基因座包含两个α-食糜酶和两个组织蛋白酶G基因，而所有其他研究的食糜酶基因座都具有单个基因。此外，牛基因座至少含有四个十二指肠酶基因，这是其他食糜酶基因座中没有发现的。有趣的是，十二指肠酶似乎具有消化功能而不是免疫功能。另一方面，在负鼠中，仅发现了两个与食糜酶基因座相关的基因。这两个基因并未排列在一个基因座上，而是似乎被有袋动物特异性的染色体重排分开。系统发育分析将负鼠基因之一与肥大细胞α-食糜酶牢牢地联系在一起，这表明在有袋动物和胎盘哺乳动物分离之前，α-食糜酶已经进化为一个单独的、可清晰识别的基因。相比之下，负鼠的第二个基因在系统发育上位于颗粒酶、组织蛋白酶 G 和十二指肠酶之间。因此，在胎盘哺乳动物与有袋动物分离后，这些基因可能进化为单独的亚科。在鸭嘴兽中，只能鉴定出一种食糜酶基因座样序列。这种先前发表的“颗粒酶”并不与任何食糜酶基因座基因家族清楚地聚类，但与其他食糜酶基因座蛋白酶共享缺乏Cys(191)-Cys(220)桥。这些发现表明，所有食糜酶基因座基因均源自 2 亿多年前就存在的单一祖先。
The acidic granules of natural killer (NK) cells, T cells, mast cells, and neutrophils store large amounts of serine proteases. Functionally, these proteases are involved, e.g., in the induction of apoptosis, the recruitment of inflammatory cells, and the remodeling of extra-cellular matrix. Among the granule proteases are the phylogenetically related mast cell chymases, neutrophil cathepsin G, and T-cell granzymes (Gzm B to H and Gzm N), which share the characteristic absence of a Cys(191)-Cys(220) bridge. The genes of these proteases are clustered in one locus, the mast cell chymase locus, in all previously investigated mammals. In this paper, we present a detailed analysis of the chymase locus in cattle (Bos taurus) and opossum (Monodelphis domestica). The gained information delineates the evolution of the chymase locus over more than 200 million years. Surprisingly, the cattle chymase locus contains two alpha-chymase and two cathepsin G genes where all other studied chymase loci have single genes. Moreover, the cattle locus holds at least four genes for duodenases, which are not found in other chymase loci. Interestingly, duodenases seem to have digestive rather than immune functions. In opossum, on the other hand, only two chymase locus-related genes have been identified. These two genes are not arranged in one locus, but appear to have been separated by a marsupial-specific chromosomal rearrangement. Phylogenetic analyses place one of the opossum genes firmly with mast cell alpha-chymases, which indicates that the alpha-chymase had already evolved as a separate, clearly identifiable gene before the separation of marsupials and placental mammals. In contrast, the second gene in opossum is positioned phylogenetically between granzymes, cathepsin G, and the duodenases. These genes, therefore, probably evolved as separate subfamilies after the separation of placental mammals from marsupials. In platypus, only one chymase locus-like sequence could be identified. This previously published "granzyme" does not cluster clearly with any of the chymase locus gene families, but shares the absence of the Cys(191)-Cys(220) bridge with the other chymase locus proteases. These findings indicate that all chymase locus genes are derived from a single ancestor that was present more than 200 million years ago.