Johnsen A H, Jonson L, Rourke I J, Rehfeld J F
Department of Clinical Biochemistry, Rigshospitalet (National University Hospital), Copenhagen, Denmark.
Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10221-6. doi: 10.1073/pnas.94.19.10221.
The peptide hormone gastrin was long believed to be specific for higher vertebrates, whereas its homologue, cholecystokinin (CCK), has been assumed to represent the original ancestor of the CCK/gastrin family. To trace the divergence of the CCK/gastrin family beyond birds, reptiles, and amphibians we have now examined sharks. Distinct CCK and gastrin peptides were identified in two shark species, the spiny dogfish (Squalus acanthias) and the porbeagle (Lamna cornubica). The corresponding genes and cDNAs were isolated and sequenced from the spiny dogfish. Comparison with several vertebrate species show that the CCK gene and peptide structures have been considerably more conserved than the corresponding gastrin structures. Alignment of the dogfish prepropeptides displays similarities that support the hypothesis that they share a common ancestor. Our findings move the CCK/gastrin family segregation back to at least 350 million years ago. This event must have occurred before, or perhaps during, the evolution of cartilagenous fishes, probably concomitant with the occurrence of gastric acid secretion.
长期以来,人们一直认为肽激素胃泌素是高等脊椎动物所特有的,而其同源物胆囊收缩素(CCK)则被认为是CCK/胃泌素家族的原始祖先。为了追溯CCK/胃泌素家族在鸟类、爬行动物和两栖动物之外的分化情况,我们现在研究了鲨鱼。在两种鲨鱼——棘鲨(Squalus acanthias)和鼠鲨(Lamna cornubica)中鉴定出了不同的CCK和胃泌素肽。从棘鲨中分离并测序了相应的基因和cDNA。与几种脊椎动物物种的比较表明,CCK基因和肽结构比相应的胃泌素结构保守得多。棘鲨前体肽的比对显示出相似性,支持了它们有共同祖先的假说。我们的发现将CCK/胃泌素家族的分化至少追溯到3.5亿年前。这一事件一定发生在软骨鱼类进化之前,或者可能在其进化过程中,可能与胃酸分泌的出现同时发生。