Concomitant Duplications of Opioid Peptide and Receptor Genes before the Origin of Jawed Vertebrates

Abstract

BackgroundThe opioid system is involved in reward and pain mechanisms and consists in mammals of four receptors and several peptides. The peptides are derived from four prepropeptide genes, PENK, PDYN, PNOC and POMC, encoding enkephalins, dynorphins, orphanin/nociceptin and beta-endorphin, respectively. Previously we have described how two rounds of genome doubling (2R) before the origin of jawed vertebrates formed the receptor family.Methodology/Principal FindingsOpioid peptide gene family members were investigated using a combination of sequence-based phylogeny and chromosomal locations of the peptide genes in various vertebrates. Several adjacent gene families were investigated similarly. The results show that the ancestral peptide gene gave rise to two additional copies in the genome doublings. The fourth member was generated by a local gene duplication, as the genes encoding POMC and PNOC are located on the same chromosome in the chicken genome and all three teleost genomes that we have studied. A translocation has disrupted this synteny in mammals. The PDYN gene seems to have been lost in chicken, but not in zebra finch. Duplicates of some peptide genes have arisen in the teleost fishes. Within the prepropeptide precursors, peptides have been lost or gained in different lineages.Conclusions/SignificanceThe ancestral peptide and receptor genes were located on the same chromosome and were thus duplicated concomitantly. However, subsequently genetic linkage has been lost. In conclusion, the system of opioid peptides and receptors was largely formed by the genome doublings that took place early in vertebrate evolution.

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

“…The chromosomal locations of the CRH family genes show that they are located in two distinct paralogons: CRH1, CRH2, and UCN1 reside in the same paralogon as the previously described opioid peptide and receptor genes (Dreborg et al 2008, Sundstrom et al 2010, Larhammar et al 2015, and the UCN2 and UCN3 genes are located in the paralogon harboring the visual opsin and oxytocin/ vasopressin receptor genes (Lagman et al 2013) (Fig. 3).…”

“…For each of the CRH family members, we also identified and analyzed gene families with members in the same chromosomal regions. This showed that the CRH family genes are located in two paralogons (sets of related chromosome regions), which have been previously analyzed in detail by us, namely the paralogon that contains the opioid peptide and receptor genes (Dreborg et al 2008, Sundstrom et al 2010, Larhammar et al 2015 and the one that contains the visual opsin genes and the oxytoc in and vasopressin receptor genes (Lagman et al 2013). This allowed us to distinguish orthologs and paralogs for the CRH family genes and to deduce that the CRH fami ly duplications took place as part of the basal vertebrate tetraploidizations (with one additional copy arising in the teleost tetraploidization, see below).…”

“…Candidate genes were selected based on previous paralogon annotations of the opioid receptor and peptide genes (Sundstrom et al 2010, Larhammar et al 2015 and the visual opsin and oxytocin/vasopressin receptor genes (Lagman et al 2013). Orthologous genes were sought by querying the genome assemblies for the different species, and gene identity (ortholog vs paralog) was investigated by phylogenetic analyses following a similar procedure as described above for the CRH family members.…”

“…3). Each of these two paralogons has numerous other gene families represented on 2-4 of the chromosomes within each paralogon (Dreborg et al 2008, Sundstrom et al 2010, Lagman et al 2013, Larhammar et al 2015. Extensive conservation of gene synteny was found for several neighboring gene families in the genomes of human, chicken, and spotted gar.…”

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.…”