Irwin D M
Department of Laboratory Medicine and Pathobiology, Banting and Best Diabetes Centre, Faculty of Medicine, University of Toronto, 100 College St., ON, M5G 1L5, Toronto, Canada.
Regul Pept. 2001 Apr 2;98(1-2):1-12. doi: 10.1016/s0167-0115(00)00232-9.
The vertebrate proglucagon gene encodes glucagon, and the two glucagon-like peptides GLP-1 and GLP-2. To better understand the origin and diversification of the distinct hormonal roles of the three glucagon-like sequences encoded by the proglucagon gene, we have examined the evolution of this gene. The structure of proglucagon has been largely maintained within vertebrates. Duplication of the proglucagon gene or duplications of sequences within the proglucagon gene are rare. All proglucagon gene duplications are likely to be the result of genome duplication events. Examination of the rates of amino acid sequence evolution of each hormone reveals that they have not evolved in a uniform manner. Each hormone has evolved in an episodic fashion, suggesting that the selective constraints acting upon the sequence vary between, and within, vertebrate classes. Changes in selection on a sequence often reflect changes in the function of the sequence, such as the change in function of GLP-1 from a glucagon-like hormone in fish to an incretin in mammals. We found that the GLP-2 sequence underwent rapid sequence evolution in the early mammal lineage, therefore we have concluded that mammalian GLP-2 has acquired a new biological function that is not found in other vertebrates. Comparisons of the hormone sequences show that many amino acid residues that are functionally important in mammalian hormones are not conserved through vertebrate evolution. This observation suggests that the sequences involved in hormone action change through evolution.
脊椎动物的胰高血糖素原基因编码胰高血糖素以及两种胰高血糖素样肽，即GLP-1和GLP-2。为了更好地理解由胰高血糖素原基因编码的三种胰高血糖素样序列的独特激素作用的起源和多样化，我们研究了该基因的进化。胰高血糖素原的结构在脊椎动物中基本保持不变。胰高血糖素原基因的复制或胰高血糖素原基因内序列的复制很少见。所有胰高血糖素原基因的复制可能都是基因组复制事件的结果。对每种激素氨基酸序列进化速率的研究表明，它们并非以统一的方式进化。每种激素都是以阶段性方式进化的，这表明作用于序列的选择限制在脊椎动物类别之间以及类别内部有所不同。序列选择的变化通常反映了序列功能的变化，例如GLP-1的功能从鱼类中的一种胰高血糖素样激素转变为哺乳动物中的一种肠促胰岛素。我们发现GLP-2序列在早期哺乳动物谱系中经历了快速的序列进化，因此我们得出结论，哺乳动物的GLP-2获得了一种其他脊椎动物所没有的新生物学功能。对激素序列的比较表明，在哺乳动物激素中具有重要功能的许多氨基酸残基在脊椎动物进化过程中并不保守。这一观察结果表明，参与激素作用的序列在进化过程中发生了变化。
