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七鳃鳗胰高血糖素与胰高血糖素样肽的起源

Lamprey proglucagon and the origin of glucagon-like peptides.

作者信息

Irwin D M, Huner O, Youson J H

机构信息

Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Ontario, Canada.

出版信息

Mol Biol Evol. 1999 Nov;16(11):1548-57. doi: 10.1093/oxfordjournals.molbev.a026067.

DOI:10.1093/oxfordjournals.molbev.a026067
PMID:10555286
Abstract

We characterized two proglucagon cDNAs from the intestine of the sea lamprey Petromyzon marinus. As in other vertebrates, sea lamprey proglucagon genes encode three glucagon-like sequences, glucagon, and glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). This observation indicates that all three glucagon-like sequences encoded by the proglucagon gene originated prior to the divergence of jawed and jawless vertebrates. Estimates of the rates of evolution for the glucagon-like sequences suggest that glucagon originated first, about 1 billion years ago, while GLP-1 and GLP-2 diverged from each other about 700 MYA. The two sea lamprey intestinal proglucagon cDNAs have differing coding potential. Proglucagon I cDNA encodes the previously characterized glucagon and the glucagon-like peptide GLP-1, while proglucagon II cDNA encodes a predicted GLP-2 and, possibly, a glucagon. The existence of two proglucagon cDNAs which differ with regard to their potential to encode glucagon-like peptides suggests that the lamprey may use differential gene expression as a third mechanism, in addition to alternative proteolytic processing and mRNA splicing, to regulate the production of proglucagon-derived peptides.

摘要

我们对海七鳃鳗(Petromyzon marinus)肠道中的两个胰高血糖素原cDNA进行了特征分析。与其他脊椎动物一样,海七鳃鳗的胰高血糖素原基因编码三种胰高血糖素样序列、胰高血糖素以及胰高血糖素样肽1和2(GLP-1和GLP-2)。这一观察结果表明,胰高血糖素原基因编码的所有三种胰高血糖素样序列在有颌和无颌脊椎动物分化之前就已起源。对胰高血糖素样序列进化速率的估计表明,胰高血糖素最早起源于约10亿年前,而GLP-1和GLP-2大约在7亿年前彼此分化。海七鳃鳗肠道中的两个胰高血糖素原cDNA具有不同的编码潜力。胰高血糖素原I cDNA编码先前已鉴定的胰高血糖素和胰高血糖素样肽GLP-1,而胰高血糖素原II cDNA编码一种预测的GLP-2,可能还有一种胰高血糖素。存在两个在编码胰高血糖素样肽潜力方面不同的胰高血糖素原cDNA,这表明七鳃鳗除了可通过蛋白水解加工和mRNA剪接的替代方式外,还可能利用差异基因表达作为第三种机制来调节胰高血糖素原衍生肽的产生。

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