School of Biological Sciences, The University of Hong Kong, Hong Kong, Special Administrative Region, China.
PLoS One. 2012;7(9):e44691. doi: 10.1371/journal.pone.0044691. Epub 2012 Sep 5.
VIP and PACAP are pleiotropic peptides belonging to the secretin superfamily of brain-gut peptides and interact specifically with three receptors (VPAC(1), PAC(1) and VPAC(2)) from the class II B G protein-coupled receptor family. There is immense interest regarding their molecular evolution which is often described closely alongside gene and/or genome duplications. Despite the wide array of information available in various vertebrates and one invertebrate the tunicate, their evolutionary origins remain unresolved. Through searches of genome databases and molecular cloning techniques, the first lamprey VIP/PACAP ligands and VPAC receptors are identified from the Japanese lamprey. In addition, two VPAC receptors (VPACa/b) are identified from inshore hagfish and ligands predicted for sea lamprey. Phylogenetic analyses group these molecules into their respective PHI/VIP, PRP/PACAP and VPAC receptor families and show they resemble ancestral forms. Japanese lamprey VIP/PACAP peptides synthesized were tested with the hagfish VPAC receptors. hfVPACa transduces signal via both adenylyl cylase and phospholipase C pathways, whilst hfVPACb was only able to transduce through the calcium pathway. In contrast to the widespread distribution of VIP/PACAP ligands and receptors in many species, the agnathan PACAP and VPAC receptors were found almost exclusively in the brain. In situ hybridisation further showed their abundance throughout the brain. The range of VIP/PACAP ligands and receptors found are highly useful, providing a glimpse into the evolutionary events both at the structural and functional levels. Though representative of ancestral forms, the VIP/PACAP ligands in particular have retained high sequence conservation indicating the importance of their functions even early in vertebrate evolution. During these nascent stages, only two VPAC receptors are likely responsible for eliciting functions before evolving later into specific subtypes post-Agnatha. We also propose VIP and PACAP's first functions to predominate in the brain, evolving alongside the central nervous system, subsequently establishing peripheral functions.
VIP 和 PACAP 是多效肽，属于脑肠肽的分泌素超家族，与 II B 类 G 蛋白偶联受体家族的三种受体（VPAC(1)、PAC(1)和 VPAC(2)）特异性相互作用。人们对它们的分子进化非常感兴趣，通常将其与基因和/或基因组复制密切相关。尽管在各种脊椎动物和一种无脊椎动物——被囊动物中有大量的信息，但它们的进化起源仍未解决。通过对基因组数据库和分子克隆技术的搜索，从日本七鳃鳗中鉴定出了第一批七鳃鳗 VIP/PACAP 配体和 VPAC 受体。此外，还从近海盲鳗中鉴定出了两种 VPAC 受体（VPACa/b）和预测的海七鳃鳗配体。系统发育分析将这些分子归入各自的 PHI/VIP、PRP/PACAP 和 VPAC 受体家族，并表明它们与祖先形式相似。合成的日本七鳃鳗 VIP/PACAP 肽与盲鳗的 VPAC 受体进行了测试。hfVPACa 通过腺苷酸环化酶和磷脂酶 C 途径转导信号，而 hfVPACb 只能通过钙途径转导。与 VIP/PACAP 配体和受体在许多物种中的广泛分布形成鲜明对比的是，无颌类的 PACAP 和 VPAC 受体几乎只存在于大脑中。原位杂交进一步显示它们在整个大脑中的丰富度。发现的 VIP/PACAP 配体和受体范围非常有用，为我们提供了一个了解结构和功能水平进化事件的视角。尽管 VIP/PACAP 配体代表了祖先形式，但它们保留了高度的序列保守性，表明即使在脊椎动物进化的早期，它们的功能也非常重要。在这些早期阶段，只有两种 VPAC 受体可能负责在进化为无颌类之后引发特定的亚类之前发挥作用。我们还提出，VIP 和 PACAP 的最初功能在大脑中占主导地位，与中枢神经系统一起进化，随后在周围建立功能。
