Extensive Changes in the Expression of the Opioid Genes between Humans and ChimpanzeesCruz-Gordillo P.a · Fedrigo O.a · Wray G.A.a, b · Babbitt C.C.a
aDepartment of Biology and Institute for Genome Sciences & Policy, and bDepartment of Evolutionary Anthropology, Duke University, Durham, N.C., USA
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
The various means by which the body perceives, transmits, and resolves the experiences of pain and nociception are mediated by a host of molecules, including neuropeptides within the opioid gene signaling pathway. The peptide ligands and receptors encoded by this group of genes have been linked to behavioral disorders as well as a number of psychiatric affective disorders. Our aim was to explore the recent evolutionary history of these two gene families by taking a comparative genomics approach, specifically through a comparison between humans and chimpanzees. Our analyses indicate differential expression of these genes between the two species, more than expected based on genome-wide comparisons, indicating that differential expression is pervasive among the opioid genes. Of the 8 family members, three genes showed significant expression differences (PENK, PNOC, and OPRL1), with two others marginally significant (OPRM1 and OPRD1). Accelerated substitution rates along human and chimpanzee lineages within the putative regulatory regions of OPRM1, POMC, and PDYN between the human and chimpanzee branches are consistent with positive selection. Collectively, these results suggest that there may have been a selective advantage to modulating the expression of the opioid genes in humans compared with our closest living relatives. Information about the cognitive roles mediated by these genes in humans may help to elucidate the trait consequences of these putatively adaptive expression changes.
© 2010 S. Karger AG, Basel
Babbitt CC, Fedrigo O, et al (2010a): Both noncoding and protein-coding RNAs contribute to gene expression evolution in the primate brain. Genome Biol Evol 18:67–79.
- Babbitt CC, Silverman JS, et al (2010b): Multiple functional variants in cis modulate PDYN expression. Mol Biol Evol 27:465–479.
- Barr CS, Schwandt ML, et al (2008): Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proc Natl Acad Sci USA 105:5277–5281.
- Barrallo A, Gonzalez-Sarmiento R, et al (1998): Cloning, molecular characterization, and distribution of a gene homologous to delta opioid receptor from zebrafish (Danio rerio). Biochem Biophys Res Commun 245:544–548.
Benjamini Y, Hochberg Y (1995): Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57:289–300.
- Blanchette M, Bataille AR, et al (2006): Genome-wide computational prediction of transcriptional regulatory modules reveals new insights into human gene expression. Genome Res 16:656–668.
- Bodnar RJ (2009): Endogenous opiates and behavior: 2008. Peptides 30:2432–2479.
- Bradford CS, Walthers EA, et al (2005): Cloning, heterologous expression and pharmacological characterization of a kappa opioid receptor from the brain of the rough-skinned newt, Taricha granulosa. J Mol Endocrinol 34:809–823.
- Bradford CS, Walthers EA, et al (2006): Delta and mu opioid receptors from the brain of a urodele amphibian, the rough-skinned newt Taricha granulosa: cloning, heterologous expression, and pharmacological characterization. Gen Comp Endocrinol 146:275–290.
- Chen JC, Smith ER, et al (1993a): The opioid receptor binding of dezocine, morphine, fentanyl, butorphanol and nalbuphine. Life Sci 52:389–396.
- Chen Y, Mestek A, et al (1993b): Molecular cloning and functional expression of a mu-opioid receptor from rat brain. Mol Pharmacol 44:8–12.
- Chuang JH, Li H (2004): Functional bias and spatial organization of genes in mutational hot and cold regions in the human genome. PLoS Biol 2:E29.
- Comb M, Seeburg PH, et al (1982): Primary structure of the human Met- and Leu-enkephalin precursor and its mRNA. Nature 295:663–666.
- Cowley MA, Smart JL, et al (2001): Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480–484.
- Crawford GE, Holt IE, et al (2006): Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Genome Res 16:123–131.
- Dores RM, Lecaude S, et al (2002): Analyzing the evolution of the opioid/orphanin gene family. Mass Spectrom Rev 21:220–243.
- Drakenberg K, Nikoshkov A, et al (2006): Mu opioid receptor A118G polymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers. Proc Natl Acad Sci USA 103:7883–7888.
- Dreborg S, Sundstrom G, et al (2008): Evolution of vertebrate opioid receptors. Proc Natl Acad Sci USA 105:15487–15492.
- Edgar RC (2004): MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797.
- Fedrigo O, Warner LR, et al (2010): A pipeline to determine RT-QPCR control genes for evolutionary studies: application to primate gene expression across multiple tissues. PLoS One 5:e12545.
- Gaffney DJ, Keightley PD (2005): The scale of mutational variation in the murid genome. Genome Res 15:1086–1094.
- Gong J, Strong JA, et al (1998): Endomorphins fully activate a cloned human mu opioid receptor. FEBS Lett 439:152–156.
- Harris JI (1959): Studies on pituitary polypeptide hormones. III. The structure of alpha-melanocyte-stimulating hormone from pig pituitary glands. Biochem J 71:451–459.
- Harris JI, Roos P (1959): Studies on pituitary polypeptide hormones. I. The structure of beta-melanocyte-stimulating hormone from pig pituitary glands. Biochem J 71:434–445.
- Haygood R, Fedrigo O, et al (2007): Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution. Nat Genet 39:1140–1144.
- Hellemans J, Mortier G, et al (2007): qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data. Genome Biol 8:R19.
- Hellmann I, Zollner S, et al (2003): Selection on human genes as revealed by comparisons to chimpanzee cDNA. Genome Res 13:831–837.
- Huang CJ, Liu HF, et al (2008): Association between human opioid receptor genes polymorphisms and pressure pain sensitivity in females. Anaesthesia 63:1288–1295.
- Hurd YL (2002): Subjects with major depression or bipolar disorder show reduction of prodynorphin mRNA expression in discrete nuclei of the amygdaloid complex. Mol Psychiatry 7:75–81.
- Karolchik D, Baertsch R, et al (2003): The UCSC Genome Browser Database. Nucleic Acids Res 31:51–54.
- Keightley PD, Lercher MJ, et al (2005): Evidence for widespread degradation of gene control regions in hominid genomes. PLoS Biol 3:e42.
- Kennedy SE, Koeppe RA, et al (2006): Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Arch Gen Psychiatry 63:1199–1208.
- Khaitovich P, Hellmann I, et al (2005): Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 309:1850–1854.
- Khaitovich P, Muetzel B, et al (2004): Regional patterns of gene expression in human and chimpanzee brains. Genome Res 14:1462–1473.
- Khalap A, Bagrosky B, et al (2005): Trends in the evolution of the proenkephalin and prodynorphin genes in gnathostomes. Ann NY Acad Sci 1040:22–37.
Kondrashov FA, Rogozin IB, et al (2002): Selection in the evolution of gene duplications. Genome Biol 3:RESEARCH0008.
- Kreek MJ (1996a): Opiates, opioids and addiction. Mol Psychiatry 1:232–254.
- Kreek MJ (1996b): Opioid receptors: some perspectives from early studies of their role in normal physiology, stress responsivity, and in specific addictive diseases. Neurochem Res 21:1469–1488.
- Kreek MJ, Bart G, et al (2005): Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments. Pharmacol Rev 57:1–26.
- Liu X, Kai M, et al (2009): Computational study of the heterodimerization between mu and delta receptors. J Comput Aided Mol Des 23:321–332.
- Meng F, Taylor LP, et al (1996): Moving from the orphanin FQ receptor to an opioid receptor using four point mutations. J Biol Chem 271:32016–32020.
- Miller GM, Bendor J, et al (2004): A mu-opioid receptor single nucleotide polymorphism in rhesus monkey: association with stress response and aggression. Mol Psychiatry 9:99–108.
- Mollereau C, Parmentier M, et al (1994): ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett 341:33–38.
- Mollereau C, Simons MJ, et al (1996): Structure, tissue distribution, and chromosomal localization of the prepronociceptin gene. Proc Natl Acad Sci USA 93:8666–8670.
- Nikoshkov A, Drakenberg K, et al (2008): Opioid neuropeptide genotypes in relation to heroin abuse: dopamine tone contributes to reversed mesolimbic proenkephalin expression. Proc Natl Acad Sci USA 105:786–791.
- Nikoshkov A, Hurd YL, et al (2005): Prodynorphin transcripts and proteins differentially expressed and regulated in the adult human brain. FASEB J 19:1543–1545.
- Noda M, Teranishi Y, et al (1982): Isolation and structural organization of the human preproenkephalin gene. Nature 297:431–434.
- Ogden CA, Rich ME, et al (2004): Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders: an expanded convergent functional genomics approach. Mol Psychiatry 9:1007–1029.
- Pan YX (2005): Diversity and complexity of the mu opioid receptor gene: alternative pre-mRNA splicing and promoters. DNA Cell Biol 24:736–750.
- Panopoulou G, Poustka AJ (2005): Timing and mechanism of ancient vertebrate genome duplications – the adventure of a hypothesis. Trends Genet 21:559–567.
- Pinal-Seoane N, Martin IR, et al (2006): Characterization of a new duplicate delta-opioid receptor from zebrafish. J Mol Endocrinol 37:391–403.
- Pond SL, Frost SD, et al (2005): HyPhy: hypothesis testing using phylogenies. Bioinformatics 21:676–679.
R Development Core Team (2005): R: A Language and Environment for Statistical Computing. Vienna, R Foundation for Statistical Computing (http://www.R-project.org).
- Rockman MV, Hahn MW, et al (2005): Ancient and recent positive selection transformed opioid cis-regulation in humans. PLoS Biol 3:2208–2219.
- Rozas J, Sanchez-DelBarrio JC, et al (2003): DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19:2496–2497.
- Shabalina SA, Zaykin DV, et al (2009): Expansion of the human mu-opioid receptor gene architecture: novel functional variants. Hum Mol Genet 18:1037–1051.
- Simonin F, Befort K, et al (1994): The human delta-opioid receptor: genomic organization, cDNA cloning, functional expression, and distribution in human brain. Mol Pharmacol 46:1015–1021.
- Simonin F, Gaveriaux-Ruff C, et al (1995): ĸ-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. Proc Natl Acad Sci USA 92:7006–7010.
- Snook LA, Milligan G, et al (2008): Co-expression of mu and delta opioid receptors as receptor-G protein fusions enhances both mu and delta signalling via distinct mechanisms. J Neurochem 105:865–873.
Sonetti D, Peruzzi E, et al (2005): Endogenous morphine and ACTH association in neural tissues. Med Sci Monit 11:MS22–MS30.
- Sorek R, Ast G (2003): Intronic sequences flanking alternatively spliced exons are conserved between human and mouse. Genome Res 13:1631–1637.
- Stein C, Zollner C (2009): Opioids and sensory nerves. Handb Exp Pharmacol 194:495–518.
- Stevens CW (2009): The evolution of vertebrate opioid receptors. Front Biosci 14:1247–1269.
- Stevens CW, Brasel CM, et al (2007): Cloning and bioinformatics of amphibian mu, delta, kappa, and nociceptin opioid receptors expressed in brain tissue: evidence for opioid receptor divergence in mammals. Neurosci Lett 419:189–194.
- Sundstrom G, Dreborg S, et al (2010): Concomitant duplications of opioid peptide and receptor genes before the origin of jawed vertebrates. PLoS One 5:e10512.
- Telkov M, Geijer T, et al (1998): Human prodynorphin gene generates several tissue-specific transcripts. Brain Res 804:284–295.
- Uddin M, Wildman DE, et al (2004): Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles. Proc Natl Acad Sci USA 101:2957–2962.
- Vallender EJ, Priddy CM, et al (2008): Human expression variation in the mu-opioid receptor is paralleled in rhesus macaque. Behav Genet 38:390–395.
Vandesompele J, De Preter K, et al (2002): Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:RESEARCH0034.
- Walthers EA, Bradford CS, et al (2005): Cloning, pharmacological characterization and tissue distribution of an ORL1 opioid receptor from an amphibian, the rough-skinned newt Taricha granulosa. J Mol Endocrinol 34:247–256.
- Wong WSW, Nielsen R (2004): Detecting selection in noncoding regions of nucleotide sequences. Genetics 167:949–958.
- Wray GA, Hahn MW, et al (2003): The evolution of transcriptional regulation in eukaryotes. Mol Biol Evol 20:1377–1419.
- Xuei X, Dick D, et al (2006): Association of the kappa-opioid system with alcohol dependence. Mol Psychiatry 11:1016–1024.
Xuei X, Flury-Wetherill L, et al (2007): The opioid system in alcohol and drug dependence: family-based association study. Am J Med Genet B Neuropsychiatr Genet 144:877–884.
- Yuferov V, Ji F, et al (2009): A functional haplotype implicated in vulnerability to develop cocaine dependence is associated with reduced PDYN expression in human brain. Neuropsychopharmacology 34:1185–1197.
- Zaveri N, Polgar WE, et al (2001): Characterization of opiates, neuroleptics, and synthetic analogs at ORL1 and opioid receptors. Eur J Pharmacol 428:29–36.
- Zhang JZ, Nielsen R, et al (2005a): Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level. Mol Biol Evol 22:2472–2479.
- Zhang Y, Wang D, et al (2005b): Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem 280:32618–32624.
- Zimprich A, Kraus J, et al (2000): An allelic variation in the human prodynorphin gene promoter alters stimulus-induced expression. J Neurochem 74:472–477.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.