scholarly journals Evolution of vertebrate opioid receptors

2008 ◽  
Vol 105 (40) ◽  
pp. 15487-15492 ◽  
Author(s):  
Susanne Dreborg ◽  
Görel Sundström ◽  
Tomas A. Larsson ◽  
Dan Larhammar
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Phylogenetic Analyses ◽  
Receptor Gene ◽  
Gene Families ◽  
Opioid Peptide ◽  
Gene Duplications ◽  
Neighboring Gene ◽  
Genome Duplications ◽  
Peptide Precursor

The opioid peptides and receptors have prominent roles in pain transmission and reward mechanisms in mammals. The evolution of the opioid receptors has so far been little studied, with only a few reports on species other than tetrapods. We have investigated species representing a broader range of vertebrates and found that the four opioid receptor types (delta, kappa, mu, and NOP) are present in most of the species. The gene relationships were deduced by using both phylogenetic analyses and chromosomal location relative to 20 neighboring gene families in databases of assembled genomes. The combined results show that the vertebrate opioid receptor gene family arose by quadruplication of a large chromosomal block containing at least 14 other gene families. The quadruplication seems to coincide with, and, therefore, probably resulted from, the two proposed genome duplications in early vertebrate evolution. We conclude that the quartet of opioid receptors was already present at the origin of jawed vertebrates ≈450 million years ago. A few additional opioid receptor gene duplications have occurred in bony fishes. Interestingly, the ancestral receptor gene duplications coincide with the origin of the four opioid peptide precursor genes. Thus, the complete vertebrate opioid system was already established in the first jawed vertebrates.

scholarly journals A Screen for Gene Paralogies Delineating Evolutionary Branching Order of Early Metazoa

2019 ◽  
Vol 10 (2) ◽  
pp. 811-826 ◽  
Author(s):  
Albert Erives ◽  
Bernd Fritzsch
Keyword(s):  
Phylogenetic Analyses ◽  
Gene Families ◽  
Single Copy ◽  
Gene Duplications ◽  
Nervous Systems ◽  
Evolutionary Diversification ◽  
Transmembrane Channel ◽  
Sensory Epithelia ◽  
Protein X ◽  
Ancient Gene

The evolutionary diversification of animals is one of Earth’s greatest marvels, yet its earliest steps are shrouded in mystery. Animals, the monophyletic clade known as Metazoa, evolved wildly divergent multicellular life strategies featuring ciliated sensory epithelia. In many lineages epithelial sensoria became coupled to increasingly complex nervous systems. Currently, different phylogenetic analyses of single-copy genes support mutually-exclusive possibilities that either Porifera or Ctenophora is sister to all other animals. Resolving this dilemma would advance the ecological and evolutionary understanding of the first animals and the evolution of nervous systems. Here we describe a comparative phylogenetic approach based on gene duplications. We computationally identify and analyze gene families with early metazoan duplications using an approach that mitigates apparent gene loss resulting from the miscalling of paralogs. In the transmembrane channel-like (TMC) family of mechano-transducing channels, we find ancient duplications that define separate clades for Eumetazoa (Placozoa + Cnidaria + Bilateria) vs. Ctenophora, and one duplication that is shared only by Eumetazoa and Porifera. In the Max-like protein X (MLX and MLXIP) family of bHLH-ZIP regulators of metabolism, we find that all major lineages from Eumetazoa and Porifera (sponges) share a duplicated gene pair that is sister to the single-copy gene maintained in Ctenophora. These results suggest a new avenue for deducing deep phylogeny by choosing rather than avoiding ancient gene paralogies.

scholarly journals Ancient Genome Duplications Did Not Structure the Human Hox-Bearing Chromosomes

2001 ◽  
Vol 11 (5) ◽  
pp. 771-780 ◽  
Author(s):  
Austin L. Hughes ◽  
Jack da Silva ◽  
Robert Friedman
Keyword(s):  
Phylogenetic Analysis ◽  
Gene Duplication ◽  
Genome Duplication ◽  
Gene Families ◽  
Gene Duplications ◽  
Human Chromosomes ◽  
Time Period ◽  
Genome Duplications

The fact that there are four homeobox (Hox) clusters in most vertebrates but only one in invertebrates is often cited as evidence for the hypothesis that two rounds of genome duplication by polyploidization occurred early in vertebrate history. In addition, it has been observed in humans and other mammals that numerous gene families include paralogs on two or more of the fourHox-bearing chromosomes (the chromosomes bearing theHox clusters; i.e., human chromosomes 2, 7, 12, and 17), and the existence of these paralogs has been taken as evidence that these genes were duplicated along with the Hox clusters by polyploidization. We tested this hypothesis by phylogenetic analysis of 42 gene families including members on two or more of the humanHox-bearing chromosomes. In 32 of these families there was evidence against the hypothesis that gene duplication occurred simultaneously with duplication of the Hox clusters. Phylogenies of 14 families supported the occurrence of one or more gene duplications before the origin of vertebrates, and of 15 gene duplication times estimated for gene families evolving in a clock-like manner, only six were dated to the same time period early in vertebrate history during which the Hox clusters duplicated. Furthermore, of gene families duplicated around the same time as the Hoxclusters, the majority showed topologies inconsistent with their having duplicated simultaneously with the Hox clusters. The results thus indicate that ancient events of genome duplication, if they occurred at all, did not play an important role in structuring the mammalian Hox-bearing chromosomes.

scholarly journals A screen for gene paralogies delineating evolutionary branching order of early Metazoa

2019 ◽  
Author(s):  
Albert Erives ◽  
Bernd Fritzsch
Keyword(s):  
Phylogenetic Analyses ◽  
Gene Families ◽  
Single Copy ◽  
Gene Duplications ◽  
Nervous Systems ◽  
Evolutionary Diversification ◽  
Transmembrane Channel ◽  
Sensory Epithelia ◽  
Ancient Gene ◽  
Early Metazoan

The evolutionary diversification of animals is one of Earth’s greatest triumphs, yet its origins are still shrouded in mystery. Animals, the monophyletic clade known as Metazoa, evolved wildly divergent multicellular life strategies featuring ciliated sensory epithelia. In many lineages epithelial sensoria became coupled to increasingly complex nervous systems. Currently, different phylogenetic analyses of single-copy genes support mutually-exclusive possibilities that either Porifera or Ctenophora is sister to all other animals. Resolving this dilemma would advance the ecological and evolutionary understanding of the first animals and the evolution of nervous systems. Here we describe a comparative phylogenetic approach based on gene duplications. We computationally identify and analyze gene families with early metazoan duplications using an approach that mitigates apparent gene loss resulting from the miscalling of paralogs. In the transmembrane channel-like (TMC) family of mechano-transducing channels, we find ancient duplications that define separate clades for Eumetazoa (Placozoa + Cnidaria + Bilateria) versus Ctenophora, and one duplication that is shared only by Eumetazoa and Porifera. In the MLX/MLXIP family of bHLH-ZIP regulators of metabolism, we find that all major lineages from Eumetazoa and Porifera (sponges) share a duplication, absent in Ctenophora. These results suggest a new avenue for deducing deep phylogeny by choosing rather than avoiding ancient gene paralogies.

scholarly journals Biased Opioid Ligands

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4257 ◽  
Author(s):  
Abdelfattah Faouzi ◽  
Balazs R. Varga ◽  
Susruta Majumdar
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Signal Transduction Pathway ◽  
Opioid Peptide ◽  
Nop Receptor ◽  
Biased Agonism ◽  
Opioid Ligands ◽  
Substance Abuse Disorders ◽  
Δ Opioid Receptor

Achieving effective pain management is one of the major challenges associated with modern day medicine. Opioids, such as morphine, have been the reference treatment for moderate to severe acute pain not excluding chronic pain modalities. Opioids act through the opioid receptors, the family of G-protein coupled receptors (GPCRs) that mediate pain relief through both the central and peripheral nervous systems. Four types of opioid receptors have been described, including the μ-opioid receptor (MOR), κ-opioid receptor (KOR), δ-opioid receptor (DOR), and the nociceptin opioid peptide receptor (NOP receptor). Despite the proven success of opioids in treating pain, there are still some inherent limitations. All clinically approved MOR analgesics are associated with adverse effects, which include tolerance, dependence, addiction, constipation, and respiratory depression. On the other hand, KOR selective analgesics have found limited clinical utility because they cause sedation, anxiety, dysphoria, and hallucinations. DOR agonists have also been investigated but they have a tendency to cause convulsions. Ligands targeting NOP receptor have been reported in the preclinical literature to be useful as spinal analgesics and as entities against substance abuse disorders while mixed MOR/NOP receptor agonists are useful as analgesics. Ultimately, the goal of opioid-related drug development has always been to design and synthesize derivatives that are equally or more potent than morphine but most importantly are devoid of the dangerous residual side effects and abuse potential. One proposed strategy is to take advantage of biased agonism, in which distinct downstream pathways can be activated by different molecules working through the exact same receptor. It has been proposed that ligands not recruiting β-arrestin 2 or showing a preference for activating a specific G-protein mediated signal transduction pathway will function as safer analgesic across all opioid subtypes. This review will focus on the design and the pharmacological outcomes of biased ligands at the opioid receptors, aiming at achieving functional selectivity.

Evolutionary relationships of the Tas2r receptor gene families in mouse and human

2003 ◽  
Vol 14 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Caroline Conte ◽  
Martin Ebeling ◽  
Anne Marcuz ◽  
Patrick Nef ◽  
Pedro J. Andres-Barquin
Keyword(s):  
Bitter Taste ◽  
Phylogenetic Analyses ◽  
Receptor Gene ◽  
Taste Receptor ◽  
Gene Families ◽  
Water Soluble ◽  
Taste Perception ◽  
Molecular Events ◽  
Human Genomes ◽  
Species Specific

The early molecular events in the perception of bitter taste start with the binding of specific water-soluble molecules to G protein-coupled receptors (GPCRs) encoded by the Tas2r family of taste receptor genes. The identification of the complete TAS2R receptor family repertoire in mouse and a comparative study of the Tas2r gene families in mouse and human might help to better understand bitter taste perception. We have identified, cloned, and characterized 13 new mouse Tas2r sequences, 9 of which encode putative functional bitter taste receptors. The encoded proteins are between 293 and 333 amino acids long and share between 18% and 54% sequence identity with other mouse TAS2R proteins. Including the 13 sequences identified, the mouse Tas2r family contains ∼30% more genes and 60% fewer pseudogenes than the human TAS2R family. Sequence and phylogenetic analyses of the proteins encoded by all mouse and human Tas2r genes indicate that TAS2R proteins present a lower degree of sequence conservation in mouse than in human and suggest a classification in five groups that may reflect a specialization in their functional activity to detect bitter compounds. Tas2r genes are organized in clusters in both mouse and human genomes, and an analysis of these clusters and phylogenetic analyses indicates that the five TAS2R protein groups were present prior to the divergence of the primate and rodent lineages. However, differences in subsequent evolutionary processes, including local duplications, interchromosomal duplications, divergence, and deletions, gave rise to species-specific sequences and shaped the diversity of the current TAS2R receptor families during mouse and human evolution.

Quantitative autoradiographic mapping of μ-, δ- and κ-opioid receptors in knockout mice lacking the μ-opioid receptor gene

1997 ◽  
Vol 778 (1) ◽  
pp. 73-88 ◽  
Author(s):  
Ian Kitchen ◽  
Susan J Slowe ◽  
Hans W.D Matthes ◽  
Brigitte Kieffer
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Knockout Mice ◽  
Receptor Gene ◽  
Μ Opioid Receptor

Quantitative autoradiographic mapping of opioid receptors in the brain of δ-opioid receptor gene knockout mice

2002 ◽  
Vol 945 (1) ◽  
pp. 9-19 ◽  
Author(s):  
Robin J Goody ◽  
Sarah M Oakley ◽  
Dominique Filliol ◽  
Brigitte L Kieffer ◽  
Ian Kitchen
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Knockout Mice ◽  
Gene Knockout ◽  
Receptor Gene ◽  
Gene Knockout Mice ◽  
Δ Opioid Receptor ◽  
The Brain

Exploring μ-Opioid Receptor Splice Variants as a Specific Molecular Target for New Analgesics

2020 ◽  
Vol 20 (31) ◽  
pp. 2866-2877
Author(s):  
Hirokazu Mizoguchi ◽  
Hideaki Fujii
Keyword(s):  
Side Effects ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Analgesic Effect ◽  
Splice Variants ◽  
Receptor Gene ◽  
Molecular Target ◽  
Μ Opioid Receptor ◽  
Dependence Liability ◽  
Μ Opioid Receptors

Since a μ-opioid receptor gene containing multiple exons has been identified, the variety of splice variants for μ-opioid receptors have been reported in various species. Amidino-TAPA and IBNtxA have been discovered as new analgesics with different pharmacological profiles from morphine. These new analgesics show a very potent analgesic effect but do not have dependence liability. Interestingly, these analgesics show the selectivity to the morphine-insensitive μ-opioid receptor splice variants. The splice variants, sensitive to these new analgesics but insensitive to morphine, may be a better molecular target to develop the analgesics without side effects.

scholarly journals Multiple ancestral and a plethora of recent gene duplications during the evolution of the green sensitive opsin genes (RH2) in teleost fishes

2021 ◽  
Author(s):  
Zuzana Musilova ◽  
Fabio Cortesi
Keyword(s):  
Evolutionary History ◽  
Gene Families ◽  
Gene Duplications ◽  
Teleost Fishes ◽  
Cone Opsin ◽  
Genomic Tools ◽  
Genome Duplications ◽  
History Of ◽  
Modern Genomic ◽  
Almost All

Vertebrates have four visual cone opsin classes that, together with a light-sensitive chromophore, provide sensitivity from the ultraviolet to the red wavelengths of light. The rhodopsin-like 2 (RH2) opsin is sensitive to the centre blue-green part of the spectrum, which is the most prevalent light underwater. While various vertebrate groups such as mammals and sharks have lost the RH2 gene, in teleost fishes this opsin has continued to proliferate. By investigating the genomes of 115 teleost species, we find that RH2 shows an extremely dynamic evolutionary history with repeated gene duplications, gene losses and gene conversion affecting entire orders, families and species. At least four ancestral duplications provided the substrate for todays RH2 diversity with duplications occurring in the common ancestors of Clupeocephala, Neoteleostei, and Acanthopterygii. Following these events, RH2 has continued to duplicate both in tandem and during lineage specific genome duplications. However, it has also been lost many times over so that in the genomes of extant teleosts, we find between zero to eight RH2 copies. Using retinal transcriptomes in a phylogenetic representative dataset of 30 species, we show that RH2 is expressed as the dominant green-sensitive opsin in almost all fish lineages. The exceptions are the Osteoglossomorpha (bony tongues and mooneyes) and several characin species that have lost RH2, and tarpons, other characins and gobies which do not or only lowly express the gene. These fishes instead express a green-shifted long-wavelength-sensitive LWS opsin. Our study highlights the strength of using modern genomic tools within a comparative framework to elucidate the detailed evolutionary history of gene families.

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