Centre of Marine Sciences, Universidade do Algarve, Faro, Portugal.
BMC Evol Biol. 2010 May 6;10:135. doi: 10.1186/1471-2148-10-135.
The secretin family is a pleotropic group of brain-gut peptides with affinity for class 2 G-protein coupled receptors (secretin family GPCRs) proposed to have emerged early in the metazoan radiation via gene or genome duplications. In human, 10 members exist and sequence and functional homologues and ligand-receptor pairs have been characterised in representatives of most vertebrate classes. Secretin-like family GPCR homologues have also been isolated in non-vertebrate genomes however their corresponding ligands have not been convincingly identified and their evolution remains enigmatic.
In silico sequence comparisons failed to retrieve a non-vertebrate (porifera, cnidaria, protostome and early deuterostome) secretin family homologue. In contrast, secretin family members were identified in lamprey, several teleosts and tetrapods and comparative studies revealed that sequence and structure is in general maintained. Sequence comparisons and phylogenetic analysis revealed that PACAP, VIP and GCG are the most highly conserved members and two major peptide subfamilies exist; i) PACAP-like which includes PACAP, PRP, VIP, PH, GHRH, SCT and ii) GCG-like which includes GCG, GLP1, GLP2 and GIP. Conserved regions flanking secretin family members were established by comparative analysis of the Takifugu, Xenopus, chicken and human genomes and gene homologues were identified in nematode, Drosophila and Ciona genomes but no gene linkage occurred. However, in Drosophila and nematode genes which flank vertebrate secretin family members were identified in the same chromosome.
Receptors of the secretin-like family GPCRs are present in protostomes but no sequence homologues of the vertebrate cognate ligands have been identified. It has not been possible to determine when the ligands evolved but it seems likely that it was after the protostome-deuterostome divergence from an exon that was part of an existing gene or gene fragment by rounds of gene/genome duplication. The duplicate exon under different evolutionary pressures originated the chordate PACAP-like and GCG-like subfamily groups. This event occurred after the emergence of the metazoan secretin GPCRs and led to the establishment of novel peptide-receptor interactions that contributed to the generation of novel physiological functions in the chordate lineage.
分泌素家族是一组具有亲和力的脑肠肽，与 2 类 G 蛋白偶联受体（分泌素家族 GPCR）结合，据推测，这些受体是通过基因或基因组复制，在后生动物辐射早期出现的。在人类中，存在 10 个成员，并且在大多数脊椎动物类群的代表中，已经鉴定出了序列和功能同源物以及配体-受体对。分泌素样家族 GPCR 同源物也已在非脊椎动物基因组中分离出来，但其相应的配体尚未得到令人信服的鉴定，其进化仍扑朔迷离。
计算机序列比较未能从海绵动物、刺胞动物、原口动物和早期后口动物中检索到非脊椎动物分泌素家族同源物。相反，在七鳃鳗、几种硬骨鱼和四足动物中鉴定出了分泌素家族成员，比较研究表明，序列和结构通常得以维持。序列比较和系统发育分析表明，PACAP、VIP 和 GCG 是最保守的成员，存在两个主要的肽亚家族；i）PACAP 样，包括 PACAP、PRP、VIP、PH、GHRH、SCT；ii）GCG 样，包括 GCG、GLP1、GLP2 和 GIP。通过比较分析 Takifugu、Xenopus、鸡和人类基因组，确定了分泌素家族成员周围的保守区域，并在线虫、果蝇和 Ciona 基因组中鉴定出了基因同源物，但没有基因连锁。然而，在果蝇和线虫中，与脊椎动物分泌素家族成员相对应的基因被鉴定为同一染色体上的基因。
原口动物中存在分泌素样家族 GPCR 受体，但尚未鉴定出脊椎动物同源配体的序列同源物。目前还无法确定配体进化的时间，但似乎很可能是在原口动物与后口动物从一个现有基因或基因片段的exon 分支之后进化而来的，exon 经过了几轮基因/基因组复制。在不同进化压力下的重复 exon 起源于脊索动物的 PACAP 样和 GCG 样亚家族。这一事件发生在后生动物分泌素 GPCR 出现之后，导致了新型肽-受体相互作用的建立，这为脊索动物谱系中新的生理功能的产生做出了贡献。
