Expansion of Secretin-Like G Protein-Coupled Receptors and Their Peptide Ligands via Local Duplications Before and After Two Rounds of Whole-Genome Duplication

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.

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

“…Interestingly, both of the CRH subfamilies are linked to GATA family members as noted previously (Hwang et al 2013). Our phylogenetic analysis shows that GATA too forms two distinct subfamilies, one consisting of GATA1, 2, and 3 and the other containing GATA 4, 5, and 6 ( Supplementary Fig.…”

“…The CRH/DH-like peptides bind and activate a group of receptors that belong to class B of the G-proteincoupled receptors (GPCRs) (Hwang et al 2013, Cardoso et al 2014, Lovejoy et al 2014. Vertebrates usually have two highly conserved CRH receptors (CRHR1 and CRHR2) that arose by gene duplication in the two rounds of basal vertebrate genome doubling (Cardoso et al 2014), the so-called 1R and 2R events (Nakatani et al 2007, Putnam et al 2008.…”

“…Subsequently, the second tetraploidization generated the extant quartet (Lovejoy & de Lannoy 2013, Lovejoy et al 2014). The other model put forth by Hwang and coworkers is based on the chromosomal locations of the four peptide genes in two separate paralogons (Hwang et al 2013). A paralogon is a set of related chromosomes or chromosome regions, usually resulting from a tetraploidization.…”

“…Vertebrate paralogons typically have four chromosome members in each paralogon as a consequence of the two tetraploidizations (1R and 2R) (Nakatani et al 2007, Putnam et al 2008, and as many as eight members in teleost fish due to their third tetraploidization (3R) (Jaillon et al 2004). Hwang and coworkers suggested that the two ancestral CRH/UCN1 and UCN2/UCN3 precursor genes arose before the vertebrate tetraploidizations and ended up on separate chromosomes, whereupon each chromosome was quadrupled in the tetraploidizations, but only two peptide genes survived in each paralogon resulting in the four peptide genes that were included in their study, (Figure 4 in Hwang et al 2013). Their analysis did not consider the CRH-like peptide previously identified in cartilaginous fish, initially proposed to have arisen early in this lineage (Nock et al 2011).…”

Comprehensive, structurally-curated alignment and phylogeny of vertebrate biogenic amine receptors

“…Although the substitution process is key for understanding GPCR evolution, fully classifiying relationships among GPCR families requires some understanding of how these radical domain changes occur. Therefore, additional approaches, such as syntenic analyses (Sundstrom et al, 2010;Widmark et al, 2011;Yegorov and Good, 2012;Hwang et al, 2013), combined with the phylogeny presented here should prove useful towards resolving the complete evolutionary history of vertebrate biogenic amine receptors.…”