Molecular evolution of CRH and CRHR subfamily before the evolutionary origin of vertebrate.

Corticotropin-releasing hormone (CRH) is well-cited for its important role in governing the stress responses via neuroendocrine system in vertebrates. After the identification of homologs of CRH receptor (CRHR) in both deuterostome and arthropod lineages, it was suggested that the ancestral homolog of CRH-CRHR molecular system is present in the bilaterian. However, homolog sequences from arthropods differ considerably from vertebrate CRH-like peptide sequences. Due to the significant difference between the biological system, as well as the gene regulatory network, of protostome and that of vertebrate, physiological studies on the protostomes may not provide important insight into the evolutionary history of vertebrate CRH system, while tunicate and amphioxus, two close relatives to vertebrate, which have diverged before two rounds of whole genome duplication (2WGDs) do. Given the identification of amphioxus CRH-like peptide by our group, this review aims to reexamine the current hypotheses on the evolution of CRH subfamily. It is generally accepted that paralogs of CRH and CRHR have been produced through 2WGDs, which occurred during the early vertebrate evolution. The identification of a single crh-like gene in amphioxi and tunicates by in silico search and the presence of two paralogons with a total of 5 crh-like genes in gnathostomes has shown that an additional duplication event might have happened to the ancestral crh-like gene before 2WGDs. On the other hand, the evolution of crhr gene subfamily appears to be mainly influenced by 2WGDs and only two receptor genes have been retained in the genomes of jawed vertebrates.