Ocampo Daza Daniel, Larhammar Dan
Department of Neuroscience, Science for Life Laboratory, Uppsala University, Box 593, SE-75124 Uppsala, Sweden.
Department of Neuroscience, Science for Life Laboratory, Uppsala University, Box 593, SE-75124 Uppsala, Sweden.
Gen Comp Endocrinol. 2018 Feb 1;257:143-160. doi: 10.1016/j.ygcen.2017.06.021. Epub 2017 Jun 23.
The receptors for the pituitary hormones growth hormone (GH), prolactin (PRL) and somatolactin (SL), and the hematopoietic hormones erythropoietin (EPO) and thrombopoietin (TPO), comprise a structurally related family in the superfamily of cytokine class-I receptors. GH, PRL and SL receptors have a wide variety of effects in development, osmoregulation, metabolism and stimulation of growth, while EPO and TPO receptors guide the production and differentiation of erythrocytes and thrombocytes, respectively. The evolution of the receptors for GH, PRL and SL has been partially investigated by previous reports suggesting different time points for the hormone and receptor gene duplications. This raises questions about how hormone-receptor partnerships have emerged and evolved. Therefore, we have investigated in detail the expansion of this receptor family, especially in relation to the basal vertebrate (1R, 2R) and teleost (3R) tetraploidizations. Receptor family genes were identified in a broad range of vertebrate genomes and investigated using a combination of sequence-based phylogenetic analyses and comparative genomic analyses of synteny. We found that 1R most likely generated EPOR/TPOR and GHR/PRLR ancestors; following this, 2R resulted in EPOR and TPOR genes. No GHR/PRLR duplicate seems to have survived after 2R. Instead the single GHR/PRLR underwent a local duplication sometime after 2R, generating separate syntenic genes for GHR and PRLR. Subsequently, 3R duplicated the gene pair in teleosts, resulting in two GHR and two PRLR genes, but no EPOR or TPOR duplicates. These analyses help illuminate the evolution of the regulatory mechanisms for somatic growth, metabolism, osmoregulation and hematopoiesis in vertebrates.
垂体激素生长激素（GH）、催乳素（PRL）和生长抑素（SL）的受体，以及造血激素促红细胞生成素（EPO）和血小板生成素（TPO）的受体，在细胞因子I类受体超家族中构成一个结构相关的家族。GH、PRL和SL受体在发育、渗透调节、代谢和生长刺激方面具有多种作用，而EPO和TPO受体分别指导红细胞和血小板的产生与分化。先前的报道对GH、PRL和SL受体的进化进行了部分研究，这些报道暗示了激素和受体基因重复的不同时间点。这引发了关于激素-受体伙伴关系如何出现和进化的问题。因此，我们详细研究了这个受体家族的扩展，特别是与基础脊椎动物（1R、2R）和硬骨鱼（3R）四倍体化的关系。在广泛的脊椎动物基因组中鉴定出受体家族基因，并结合基于序列的系统发育分析和共线性的比较基因组分析进行研究。我们发现1R最有可能产生EPOR/TPOR和GHR/PRLR的祖先；在此之后，2R产生了EPOR和TPOR基因。2R之后似乎没有GHR/PRLR的重复基因存活下来。相反，单个GHR/PRLR在2R之后的某个时间经历了局部重复，产生了GHR和PRLR的独立共线基因。随后，3R在硬骨鱼中复制了基因对，产生了两个GHR和两个PRLR基因，但没有EPOR或TPOR的重复基因。这些分析有助于阐明脊椎动物体细胞生长、代谢、渗透调节和造血调控机制的进化。
