Roch Graeme J, Sherwood Nancy M
Department of Biology, University of Victoria, British Columbia, Canada.
Department of Biology, University of Victoria, British Columbia, Canada
Genome Biol Evol. 2014 Jun 5;6(6):1466-79. doi: 10.1093/gbe/evu118.
The cystine knot growth factor (CKGF) superfamily includes important secreted developmental regulators, including the families of transforming growth factor beta, nerve growth factor, platelet-derived growth factor, and the glycoprotein hormones (GPHs). The evolutionary origin of the GPHs and the related invertebrate bursicon hormone, and their characteristic receptors, contributes to an understanding of the endocrine system in metazoans. Using a sensitive search method with hidden Markov models, we identified homologs of the hormones and receptors, along with the closely related bone morphogenetic protein (BMP) antagonists in basal metazoans. In sponges and a comb jelly, cystine knot hormones (CKHs) with mixed features of GPHs, bursicon, and BMP antagonists were identified using primary sequence and phylogenetic analysis. Also, we identified potential receptors for these CKHs, leucine-rich repeat-containing G protein-coupled receptors (LGRs), in the same species. Cnidarians, such as the sea anemone, coral, and hydra, diverged later in metazoan evolution and appear to have duplicated and differentiated CKH-like peptides resulting in bursicon/GPH-like peptides and several BMP antagonists: Gremlin (Grem), sclerostin domain containing (SOSD), neuroblastoma suppressor of tumorigenicity 1 (NBL1), and Norrie disease protein. An expanded cnidarian LGR group also evolved, including receptors for GPH and bursicon. With the appearance of bilaterians, a separate GPH (thyrostimulin) along with bursicon and BMP antagonists were present. Synteny indicates that the GPHs, Grem, and SOSD have been maintained in a common gene neighborhood throughout much of metazoan evolution. The stable and highly conserved CKGFs are not identified in nonmetazoan organisms but are established with their receptors in the basal metazoans, becoming critical to growth, development, and regulation in all animals.
胱氨酸结生长因子（CKGF）超家族包括重要的分泌型发育调节因子，其中有转化生长因子β家族、神经生长因子家族、血小板衍生生长因子家族以及糖蛋白激素（GPHs）家族。GPHs以及相关的无脊椎动物羽化激素及其特征性受体的进化起源，有助于我们理解后生动物的内分泌系统。利用基于隐马尔可夫模型的灵敏搜索方法，我们在基础后生动物中鉴定出了这些激素和受体的同源物，以及与之密切相关的骨形态发生蛋白（BMP）拮抗剂。在海绵动物和栉水母中，通过一级序列和系统发育分析，鉴定出了具有GPHs、羽化激素和BMP拮抗剂混合特征的胱氨酸结激素（CKHs）。此外，我们在同一物种中鉴定出了这些CKHs的潜在受体，即富含亮氨酸重复序列的G蛋白偶联受体（LGRs）。刺胞动物，如海葵、珊瑚和水螅，在动物进化过程中分化较晚，似乎已经复制并分化出了CKH样肽，产生了羽化激素/GPH样肽以及几种BMP拮抗剂：Gremlin（Grem）、含硬化蛋白结构域（SOSD）、致瘤性神经母细胞瘤抑制因子1（NBL1）和诺里病蛋白。刺胞动物中一个扩大的LGR组也进化出来了，包括GPH和羽化激素的受体。随着两侧对称动物出现，单独的GPH（促甲状腺素）以及羽化激素和BMP拮抗剂也出现了。共线性分析表明，在整个后生动物进化的大部分过程中，GPHs、Grem和SOSD一直存在于一个共同的基因邻域中。稳定且高度保守的CKGFs在非后生动物中未被发现，但在基础后生动物中与它们的受体一起建立起来，对所有动物的生长、发育和调节变得至关重要。
