No abstract

In humans, the secretin-like G protein-coupled receptor (GPCR) family comprises 15 members with 18 corresponding peptide ligand genes. Although members have been identified in a large variety of vertebrate and nonvertebrate species, the origin and relationship of these proteins remain unresolved. To address this issue, we employed large-scale genome comparisons to identify genome fragments with conserved synteny and matched these fragments to linkage groups in reconstructed early gnathostome ancestral chromosomes (GAC). This genome comparison revealed that most receptor and peptide genes were clustered in three GAC linkage groups and suggested that the ancestral forms of five peptide subfamilies (corticotropin-releasing hormone-like, calcitonin-like, parathyroid hormone-like, glucagon-like, and growth hormone-releasing hormone-like) and their cognate receptor families emerged through tandem local gene duplications before two rounds (2R) of whole-genome duplication. These subfamily genes have, then, been amplified by 2R whole-genome duplication, followed by additional local duplications and gene loss prior to the divergence of land vertebrates and teleosts. This study delineates a possible evolutionary scenario for whole secretin-like peptide and receptor family members and may shed light on evolutionary mechanisms for expansion of a gene family with a large number of paralogs.

Patients with tumors preoperatively categorized as LR-M may have a worse prognosis than those with tumors categorized LR-3, LR-4, or LR-5 after curative resection of single hepatic malignancy.

In humans, numerous genes encode neuropeptides that comprise a superfamily of more than 70 genes in approximately 30 families and act mainly through rhodopsin-like G protein-coupled receptors (GPCRs). Two rounds of whole-genome duplication (2R WGD) during early vertebrate evolution greatly contributed to proliferation within gene families; however, the mechanisms underlying the initial emergence and diversification of these gene families before 2R WGD are largely unknown. In this study, we analyzed 25 vertebrate rhodopsin-like neuropeptide GPCR families and their cognate peptides using phylogeny, synteny, and localization of these genes on reconstructed vertebrate ancestral chromosomes (VACs). Based on phylogeny, these GPCR families can be divided into five distinct clades, and members of each clade tend to be located on the same VACs. Similarly, their neuropeptide gene families also tend to reside on distinct VACs. Comparison of these GPCR genes with those of invertebrates including Drosophila melanogaster, Caenorhabditis elegans, Branchiostoma floridae, and Ciona intestinalis indicates that these GPCR families emerged through tandem local duplication during metazoan evolution prior to 2R WGD. Our study describes a presumptive evolutionary mechanism and development pathway of the vertebrate rhodopsin-like GPCR and cognate neuropeptide families from the urbilaterian ancestor to modern vertebrates.