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Molecular biology reports2026; 53(1); 1405; doi: 10.1007/s11033-026-12585-1

Comparative genomic analysis of oxytocin and oxytocin receptor genes in the family Equidae.

Abstract: The oxytocin (OXT) - oxytocin receptor (OXTR) system regulates diverse biological processes including social behavior, stress responses, and processes related to domestication. While OXT is highly conserved, OXTR shows greater variability, which may contribute to species-specific adaptations. Methods: Comparative genomic analyses of OXT and OXTR coding sequences were performed across equid species using available genome assemblies and newly generated sequences obtained by next-generation sequencing. Phylogenetic relationships were inferred using maximum likelihood methods. Selection was assessed using codon-based approaches (FEL, SLAC, FUBAR). The potential effects of amino acid substitutions were predicted using in silico tools, including SIFT, Missense3D, and NetPhos. Results: The OXT gene was conserved across equids, with no variation in the amino acid sequence. The OXTR gene was more variable, with most nonsynonymous substitutions located in the C-terminal region. Predominantly purifying selection was detected, with limited diversifying selection. OXTR gene variability differed among species, being lower in horses and higher in zebras and wild asses. Differences between domesticated and nondomesticated groups were observed. Trans-species haplotype sharing and distinct patterns at amino acid positions 182 and 344 were identified. Conclusions: The OXTR gene shows genetic variability in equids, with differences between domesticated and nondomesticated species. Some variants may represent candidate markers for future studies of domestication, behavior, and comparisons between ancient and modern DNA.
Publication Date: 2026-08-14 PubMed ID: 42599569PubMed Central: 12229615DOI: 10.1007/s11033-026-12585-1Google Scholar: Lookup
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  • Journal Article
  • Comparative Study

Summary

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Comparative genomic analysis of oxytocin and oxytocin receptor genes in equids reveals that while the oxytocin gene is highly conserved, the oxytocin receptor gene exhibits genetic variability, particularly differing between domesticated and nondomesticated species.

Background and Purpose

  • The oxytocin (OXT) and oxytocin receptor (OXTR) system plays crucial roles in regulating social behaviors, stress response, and traits linked to domestication in animals.
  • Although the OXT gene is generally conserved across species, the OXTR gene shows more variability, potentially underpinning species-specific adaptations among equids (horses, zebras, wild asses).
  • The study aimed to investigate the genetic diversity and evolutionary pressures on OXT and OXTR genes across different equid species using genomic data.

Methods

  • Comparative genomic analyses were conducted on the coding sequences of the OXT and OXTR genes using publicly available equid genome assemblies and newly sequenced data from next-generation sequencing efforts.
  • Phylogenetic relationships among species were inferred using maximum likelihood methods to understand evolutionary linkages.
  • Selection pressures on genes were evaluated through codon-based models, employing methods such as FEL (Fixed Effects Likelihood), SLAC (Single-Likelihood Ancestor Counting), and FUBAR (Fast Unconstrained Bayesian AppRoximation).
  • Computational predictive tools (SIFT, Missense3D, NetPhos) were used to assess the potential functional impact of amino acid substitutions identified in OXTR sequences.

Key Findings

  • OXT Gene Conservation: The oxytocin gene showed no amino acid sequence variation across all equid species analyzed, demonstrating high conservation.
  • OXTR Gene Variability: The oxytocin receptor gene exhibited genetic variability, mainly in the C-terminal region of the encoded protein, where most nonsynonymous (amino acid-changing) substitutions were found.
  • Selection Patterns: The OXTR gene was predominantly under purifying selection, indicating evolutionary pressure to maintain its function, but some limited diversifying selection (positive selection at certain sites) was detected.
  • Species Differences:
    • Domesticated horses showed lower genetic variability in OXTR compared to nondomesticated species like zebras and wild asses, which displayed higher variability.
    • Distinct differences were noted between domesticated and nondomesticated groups in the patterns of OXTR gene variation.
  • Haplotype Sharing and Key Amino Acid Sites:
    • Some haplotypes (specific combinations of genetic variants) were shared trans-species, indicating possible conserved or ancestral variants.
    • Notable variations at amino acid positions 182 and 344 were identified, possibly linked to functional differences.

Conclusions and Implications

  • The strong conservation of the OXT gene across equids confirms its critical and stable biological role.
  • The observed variability in the OXTR gene, especially marked between domesticated and nondomesticated species, suggests that OXTR variants might have contributed to adaptations related to domestication and behavior.
  • Specific OXTR variants identified in this study could serve as candidate genetic markers for future research focused on domestication processes, social behavior traits, and evolutionary comparisons using ancient and modern DNA samples.
  • This study enhances our understanding of how genetic variation in neuropeptide receptor genes might influence species-specific traits in the Equidae family.

Cite This Article

APA
Vychodilova L, Janova E, Plasil M, Futas J, Stejskalova K, Oppelt J, Horin P. (2026). Comparative genomic analysis of oxytocin and oxytocin receptor genes in the family Equidae. Mol Biol Rep, 53(1), 1405. https://doi.org/10.1007/s11033-026-12585-1

Publication

ISSN: 1573-4978
NlmUniqueID: 0403234
Country: Netherlands
Language: English
Volume: 53
Issue: 1
PII: 1405

Researcher Affiliations

Vychodilova, Leona
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, 61242, Czech Republic. vychodiloval@vfu.cz.
Janova, Eva
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, 61242, Czech Republic.
Plasil, Martin
  • RG Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czech Republic.
Futas, Jan
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, 61242, Czech Republic.
  • RG Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czech Republic.
Stejskalova, Karla
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, 61242, Czech Republic.
Oppelt, Jan
  • RG Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czech Republic.
Horin, Petr
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, 61242, Czech Republic.
  • RG Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czech Republic.

MeSH Terms

  • Animals
  • Receptors, Oxytocin / genetics
  • Oxytocin / genetics
  • Phylogeny
  • Equidae / genetics
  • Genomics / methods
  • Genetic Variation
  • Amino Acid Sequence
  • Evolution, Molecular
  • Horses / genetics
  • Haplotypes
  • Selection, Genetic

Grant Funding

  • 2024ITA32 / ITA VETUNI BRNO

Conflict of Interest Statement

Declarations. Competing interests: The authors declare no competing interests. Consent for publication: Not applicable. Ethics approval and consent to participate: All blood samples used in this study were archived samples originally collected for the purposes of other projects [13, 23]. All these samples were collected by licensed veterinarians in agreement with all ethical, welfare and professional standards. Generative AI-assisted technologies in the writing process: The authors used ChatGPT (OpenAI) for language editing and take full responsibility for the content.

References

This article includes 44 references
  1. Hoyle CH. Neuropeptide families and their receptors: evolutionary perspectives.. Brain Res 848:1–25.
    doi: 10.1016/s0006-8993(99)01975-7pubmed: 10612694google scholar: lookup
  2. Chrudinová M, DaCosta JM, Dogru D, Huang R, Reiners R, De Meyts P, Altindis E. Evolution of insulin, insulin-like growth factors, and their cognate receptors in vertebrates, invertebrates, and viruses.. Mol Biol Evol 43:msaf319.
    doi: 10.1093/molbev/msaf319google scholar: lookup
  3. Gimpl G, Fahrenholz F. The Oxytocin receptor system: Structure, function, and regulation.. Physiol Rev 81:629–683.
    doi: 10.1152/physrev.2001.81.2.629pubmed: 11274341google scholar: lookup
  4. Cui X, Xiao L. Complexity of the hypothalamic oxytocin system and its involvement in brain functions and diseases.. Neurosci Bull 41:1267–1288.
    doi: 10.1007/s12264-025-01424-1pubmed: 40445489pmc: 12229615google scholar: lookup
  5. Vargas-Pinilla P, Paixão-Côrtes VR, Paré P, Tovo-Rodrigues L, Vieira CM deAG, Xavier A, Comas D, Pissinatti A, Sinigaglia M, Rigo MM, Vieira GF, Lucion AB, Salzano FM, Bortolini MC. Evolutionary pattern in the OXT-OXTR system in primates: Coevolution and positive selection footprints.. Proc Natl Acad Sci 112:88–93.
    doi: 10.1073/pnas.1419399112pubmed: 25535371google scholar: lookup
  6. Kohlhoff J, Cibralic S, Hawes DJ, Eapen V. Oxytocin receptor gene (OXTR) polymorphisms and social, emotional and behavioral functioning in children and adolescents: A systematic narrative review.. Neurosci Biobehavioral Reviews 135:104573.
  7. Bence M, Marx P, Szantai E, Kubinyi E, Ronai Z, Banlaki Z. Lessons from the canine Oxtr gene: populations, variants and functional aspects.. Genes Brain Behav 16:427–438.
    doi: 10.1111/gbb.12356pubmed: 27860243google scholar: lookup
  8. Fam BSO, Paré P, Felkl AB, Vargas-Pinilla P, Paixão-Côrtes VR, Viscardi LH, Bortolini MC. Oxytocin and arginine vasopressin systems in the domestication process.. Genet Mol Biol 41:235–242.
  9. Yuan S, Zhang YQ. The effects of oxytocin on social behavior and eye gaze: Insights from dog-human partnership.. Neurosci Biobehav Rev 184:106602.
  10. Ahmad HI, Ahmad MJ, Jabbir F, Ahmar S, Ahmad N, Elokil AA, Chen J. The Domestication makeup: Evolution, survival, and challenges.. Front Ecol Evol 8.
    doi: 10.3389/fevo.2020.00103google scholar: lookup
  11. Steklis NG, Peñaherrera-Aguirre M, Steklis HD, Herrera I. Why were zebras not domesticated? A Review of domesticability traits and tests of their role in ungulate domestications with macroevolutionary models.. Animals 14:2355.
    doi: 10.3390/ani14162355pubmed: 39199888pmc: 11350691google scholar: lookup
  12. Orlando L. Equids.. Curr Biol 25:R973–R978.
    doi: 10.1016/j.cub.2015.09.005pubmed: 26485367google scholar: lookup
  13. Stejskalova K, Janova E, Splichalova P, Futas J, Oppelt J, Vodicka R, Horin P. Twelve toll-like receptor (TLR) genes in the family Equidae – comparative genomics, selection and evolution.. Vet Res Commun 48:725–741.
    doi: 10.1007/s11259-023-10245-4pubmed: 37874499google scholar: lookup
  14. Cerrito P, Spear JK. Lack of evidence for coevolution between oxytocin receptor N-terminal variants and monogamy in placental mammals.. Horm Behav 156:105437.
    doi: 10.1016/j.yhbeh.2023.105437pubmed: 37806189google scholar: lookup
  15. Waltenspühl Y, Ehrenmann J, Vacca S, Thom C, Medalia O, Plückthun A. Structural basis for the activation and ligand recognition of the human oxytocin receptor.. Nat Commun 13:4153.
    doi: 10.1038/s41467-022-31325-0pubmed: 35851571pmc: 9293896google scholar: lookup
  16. Feldman R, Monakhov M, Pratt M, Ebstein RP. Oxytocin pathway genes: Evolutionary ancient system impacting on human affiliation, sociality, and psychopathology.. Biol Psychiatry 79:174–184.
  17. Kis A, Bence M, Lakatos G, Pergel E, Turcsán B, Pluijmakers J, Vas J, Elek Z, Brúder I, Földi L, Sasvári-Székely M, Miklósi Á, Rónai Z, Kubinyi E. Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris).. PLoS ONE 9:e83993.
    doi: 10.1371/journal.pone.0083993pubmed: 24454713pmc: 3893090google scholar: lookup
  18. Kubinyi E, Bence M, Koller D, Wan M, Pergel E, Ronai Z, Sasvari-Szekely M, Miklosi A. Oxytocin and opioid receptor gene polymorphisms associated with greeting behavior in dogs.. Front Psychol 8:1520.
    doi: 10.3389/fpsyg.2017.01520pubmed: 28936190pmc: 5594098google scholar: lookup
  19. Kim J, Yoon M. The effect of serotonin and oxytocin on equine docility and friendliness to humans.. J Veterinary Behav 50:18–22.
  20. Wiener P, Wilkinson S. Deciphering the genetic basis of animal domestication.. Proc Royal Soc B: Biol Sci .
    doi: 10.1098/rspb.2011.1376google scholar: lookup
  21. Andersson L, Purugganan M. Molecular genetic variation of animals and plants under domestication.. Proc Natl Acad Sci 119:e2122150119.
    doi: 10.1073/pnas.2122150119pubmed: 35858409pmc: 9335317google scholar: lookup
  22. Makino T, Rubin C-J, Carneiro M, Axelsson E, Andersson L, Webster MT. Elevated proportions of deleterious genetic variation in domestic animals and plants.. Genome Biol Evol 10:276–290.
    doi: 10.1093/gbe/evy004pubmed: 29325102pmc: 5786255google scholar: lookup
  23. Klumplerova M, Splichalova P, Oppelt J, Futas J, Kohutova A, Musilova P, Kubickova S, Vodicka R, Orlando L, Horin P. Genetic diversity, evolution and selection in the major histocompatibility complex DRB and DQB loci in the family Equidae.. BMC Genomics 21:677.
    doi: 10.1186/s12864-020-07089-6pubmed: 32998693pmc: 7525986google scholar: lookup
  24. Powell HR, Islam SA, David A, Sternberg MJE. Phyre2.2: A Community resource for template-based protein structure prediction.. J Mol Biol 437:168960.
    doi: 10.1016/j.jmb.2025.168960pubmed: 40133783pmc: 7617537google scholar: lookup
  25. Ittisoponpisan S, Islam SA, Khanna T, Alhuzimi E, David A, Sternberg MJE. Can predicted protein 3D structures provide reliable insights into whether missense variants are disease associated?. J Mol Biol 431:2197–2212.
    doi: 10.1016/j.jmb.2019.04.009pubmed: 30995449pmc: 6544567google scholar: lookup
  26. Steensma MJ, Ducro BJ, Dibbits B, Doekes HP, van Schipstal JGC, Kalblfleisch T, Groenen MAM, Derks MFL. High-quality, haplotype-resolved reference genomes of the Dutch warmblood horse and Friesian horse using trio binning.. BMC Genomics 26:790.
    doi: 10.1186/s12864-025-11985-0pubmed: 40890628pmc: 12400632google scholar: lookup
  27. Wang C, Li H, Guo Y, Huang J, Sun Y, Min J, Wang J, Fang X, Zhao Z, Wang S, Zhang Y, Liu Q, Jiang Q, Wang X, Guo Y, Yang C, Wang Y, Tian F, Zhuang G, Fan Y, Gao Q, Li Y, Ju Z, Li J, Li R, Hou M, Yang G, Liu G, Liu W, Guo J, Pan S, Fan G, Zhang W, Zhang R, Yu J, Zhang X, Yin Q, Ji C, Jin Y, Yue G, Liu M, Xu J, Liu S, Jordana J, Noce A, Amills M, Wu DD, Li S, Zhou X, Zhong J. Donkey genomes provide new insights into domestication and selection for coat color.. Nat Commun 11:6014.
    doi: 10.1038/s41467-020-19813-7pubmed: 33293529pmc: 7723042google scholar: lookup
  28. Wuyun B, Liu J, Wu R, Li Y, Liu F, Zhao H, Hao C, Zhao G, Sun W, Song Y, Wang W, Wang Y, Ma C, Xu F, He J, Wang P, Bao X, Cao G, Zhang Y, Lu Y, Li X. A telomere-to-telomere gapless genome assembly of the Tibetan wild ass (Equus kiang).. Sci Data 13:182.
    doi: 10.1038/s41597-025-06494-4pubmed: 41495097pmc: 12887062google scholar: lookup
  29. Cosenza G, Iannaccone M, Pico BA, Gallo D, Capparelli R, Pauciullo A. Molecular characterisation, genetic variability and detection of a functional polymorphism influencing the promoter activity of OXT gene in goat and sheep.. J Dairy Res 84:165–169.
    doi: 10.1017/S0022029917000097pubmed: 28290268google scholar: lookup
  30. Paré P, Paixão-Côrtes VR, Tovo-Rodrigues L, Vargas-Pinilla P, Viscardi LH, Salzano FM, Henkes LE, Bortolini MC. Oxytocin and arginine vasopressin receptor evolution: implications for adaptive novelties in placental mammals.. Genet Mol Biol 39:646–657.
  31. Jaakola V-P, Prilusky J, Sussman JL, Goldman A. G protein-coupled receptors show unusual patterns of intrinsic unfolding.. Protein Eng Des Selection 18:103–110.
    doi: 10.1093/protein/gzi004google scholar: lookup
  32. Funk MW, Kidd JM. A Variant-centric analysis of allele sharing in dogs and wolves.. Genes 15.
    doi: 10.3390/genes15091168google scholar: lookup
  33. Svishcheva G, Babayan O, Sipko T, Kashtanov S, Kholodova M, Stolpovsky Y. Genetic differentiation between coexisting wild and domestic Reindeer (Rangifer tarandus L. 1758) in Northern Eurasia.. Genetic Resour 3:1–14.
    doi: 10.46265/genresj.UYML5006google scholar: lookup
  34. Zeder MA. Pathways to animal domestication.. In: Damania AB, Qualset CO, McGuire PE, Gepts P, Bettinger RL, Brush SB, Famula TR (eds) Biodiversity in Agriculture: Domestication, Evolution, and Sustainability. Cambridge University Press, Cambridge, pp 227–259.
  35. Nagasawa M, Mitsui S, En S, Ohtani N, Ohta M, Sakuma Y, Onaka T, Mogi K, Kikusui T. Oxytocin-gaze positive loop and the coevolution of human-dog bonds.. Science 348:333–336.
    doi: 10.1126/science.1261022pubmed: 25883356google scholar: lookup
  36. Azevedo L, Serrano C, Amorim A, Cooper DN. Trans-species polymorphism in humans and the great apes is generally maintained by balancing selection that modulates the host immune response.. Hum Genomics 9:21.
    doi: 10.1186/s40246-015-0043-1pubmed: 26337052pmc: 4559023google scholar: lookup
  37. Wang F, Yin X-S, Lu J, Cen C, Wang Y. Phosphorylation-dependent positive feedback on the oxytocin receptor through the kinase PKD1 contributes to long-term social memory.. Sci Signal 15:eabd0033.
    doi: 10.1126/scisignal.abd0033pubmed: 35104164google scholar: lookup
  38. Jurek B, Neumann ID. The Oxytocin receptor: From intracellular signaling to behavior.. Physiol Rev 98:1805–1908.
    doi: 10.1152/physrev.00031.2017pubmed: 29897293google scholar: lookup
  39. Jónsson H, Schubert M, Seguin-Orlando A, Ginolhac A, Petersen L, Fumagalli M, Albrechtsen A, Petersen B, Korneliussen TS, Vilstrup JT, Lear T, Myka JL, Lundquist J, Miller DC, Alfarhan AH, Alquraishi SA, Al-Rasheid KAS, Stagegaard J, Strauss G, Bertelsen MF, Sicheritz-Ponten T, Antczak DF, Bailey E, Nielsen R, Willerslev E, Orlando L. Speciation with gene flow in equids despite extensive chromosomal plasticity.. Proc Natl Acad Sci U S A 111:18655–18660.
    doi: 10.1073/pnas.1412627111pubmed: 25453089pmc: 4284605google scholar: lookup
  40. Sharif MB, Mohaseb AF, Zimmermann MI, Trixl S, Saliari K, Kunst GK, Cucchi T, Czeika S, Mashkour M, Orlando L, Schaefer K, Peters J, Mohandesan E. Ancient DNA refines taxonomic classification of Roman equids north of the Alps, elaborated with osteomorphology and geometric morphometrics.. J Archaeol Sci 143:105624.
    doi: 10.1016/j.jas.2022.105624google scholar: lookup
  41. Petersen JL, Mickelson JR, Rendahl AK, Valberg SJ, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS, Brama P, da Câmara Machado A, Capomaccio S, Cappelli K, Cothran EG, Distl O, Fox-Clipsham L, Graves KT, Guérin G, Haase B, Hasegawa T, Hemmann K, Hill EW, Leeb T, Lindgren G, Lohi H, Lopes MS, McGivney BA, Mikko S, Orr N, Penedo MCT, Piercy RJ, Raekallio M, Rieder S, Røed KH, Swinburne J, Tozaki T, Vaudin M, Wade CM, McCue ME. Genome-wide analysis reveals selection for important traits in domestic horse breeds.. PLoS Genet 9:e1003211.
    doi: 10.1371/journal.pgen.1003211pubmed: 23349635pmc: 3547851google scholar: lookup
  42. Wright D. The Genetic architecture of domestication in animals.. Bioinform Biol Insights 9:11–20.
    doi: 10.4137/BBI.S28902pubmed: 26512200pmc: 4603525google scholar: lookup
  43. Ashkenazy H, Erez E, Martz E, Pupko T, Ben-Tal N. ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids.. Nucleic Acids Res 38:W529–W533.
    doi: 10.1093/nar/gkq399pubmed: 20478830pmc: 2896094google scholar: lookup
  44. Laboy Cintrón D, Sheng RR, Ahituv N. Functional characterization of OXTR-associated enhancers.. Hum Mol Genet 34:837–842.
    doi: 10.1093/hmg/ddaf022pubmed: 39957428pmc: 12056307google scholar: lookup

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