Corticotropin-releasing hormone family evolution: five ancestral genes remain in some lineages

Abstract

The evolution of the peptide family consisting of corticotropin-releasing hormone (CRH) and the three urocortins (UCN1-3) has been puzzling due to uneven evolutionary rates. Distinct gene duplication scenarios have been proposed in relation to the two basal rounds of vertebrate genome doubling (2R) and the teleost fish-specific genome doubling (3R). By analyses of sequences and chromosomal regions, including many neighboring gene families, we show here that the vertebrate progenitor had two peptide genes that served as the founders of separate subfamilies. Then, 2R resulted in a total of five members: one subfamily consists of CRH1, CRH2, and UCN1. The other subfamily contains UCN2 and UCN3. All five peptide genes are present in the slowly evolving genomes of the coelacanth Latimeria chalumnae (a lobe-finned fish), the spotted gar Lepisosteus oculatus (a basal ray-finned fish), and the elephant shark Callorhinchus milii (a cartilaginous fish). The CRH2 gene has been lost independently in placental mammals and in teleost fish, but is present in birds (except chicken), anole lizard, and the nonplacental mammals platypus and opossum. Teleost 3R resulted in an additional surviving duplicate only for crh1 in some teleosts including zebrafish (crh1a and crh1b). We have previously reported that the two vertebrate CRH/UCN receptors arose in 2R and that CRHR1 was duplicated in 3R. Thus, we can now conclude that this peptide-receptor system was quite complex in the ancestor of the jawed vertebrates with five CRH/UCN peptides and two receptors, and that crh and crhr1 were duplicated in the teleost fish tetraploidization.

Evolution of neuropeptide signalling systems

“…The spotted gar has retained all five members ( Fig. 5 A), as has the coelacanth Latimeria chalumnae and the elephant shark Callorhinchus milii ( Cardoso et al, 2016a ), in line with the observation that these species represent lineages that seem to evolve more slowly, both with regard to amino acid sequences and overall genome organisation. The CRH2 gene was probably lost in the common ancestor of placental mammals.…”

“…However, the members were found to be located in two distinct paralogons, with two peptide genes in each. Very recently, a fifth member of the family, now named CRH2, was found to be part of one of these paralogons and, thus, to have originated in 2R ( Cardoso et al, 2016a ). Therefore, the two ancestral genes present in the vertebrate predecessor were duplicated in 2R to give rise to one triplet consisting of CRH, urocortin 1 (UCN1) and the newly discovered CRH2, and one pair consisting of UCN2 and UCN3 ( Fig.…”

Three urocortins in medaka: identification and spatial expression in the central nervous system

“…Synteny analysis of the uts1 , ucn2 and ucn3 loci was performed based on the Ensembl genome assemblies of human, mouse, Xenopus, zebrafish, fugu and medaka. The genes used for synteny analysis were selected in accordance with previous studies …”

Corticotropin-Releasing Hormone (CRH) Gene Family Duplications in Lampreys Correlate With Two Early Vertebrate Genome Doublings

“…Two are named CRH (CRH1 and 2) and three are named urocortin (UCN1, 2, and 3). They have evolved through distinct pressures during the vertebrate radiation, as reflected in their differences in evolutionary rates of amino acid change ( Hwang et al, 2013 ; Grone and Maruska, 2015b ; Cardoso et al, 2016 ; Endsin et al, 2017 ). CRH (now named CRH1) was the first family member to be discovered.…”