Analyze Diet
Journal of animal science2019; 97(4); 1578-1585; doi: 10.1093/jas/skz071

Synergy between MC1R and ASIP for coat color in horses (Equus caballus)1.

Abstract: Through domestication and human selection, horses have acquired various coat colors, including seven phenotypes: black, brown, dark bay, bay, chestnut, white, and gray. Here we determined the genotypes for melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) in 709 horses from 15 breeds. We found that the EEEE genotype frequency at MC1R decreased from dark to light colors (black = 64.5%, brown = 67.5%, dark bay = 47.0%, bay = 16.5%, and chestnut = 0.0%), whereas the AAAA genotype frequency at ASIP increased as coat color lightened (black = 0.0%, brown = 22.9%, dark bay = 69.2%, and bay = 83.0%). When combined genotypes at MC1R and ASIP were examined, different advantage genotype combinations were found for each color: black EEEE-AaAa (64.5%), brown EEEE-AAAa (47.0%), dark bay EEEE-AAAA, and EEEe-AAAA (36.2% and 33.0%, totally 69.2%), bay EEEe-AAAA (69.6%), and chestnut EeEe-AAAA (62.6%). The χ2 test showed that the phenotypes of horse coat colors were significantly related with the genotypes of MC1R and ASIP (p < 0.001). Furthermore, in contrast to a previous study where AaAa was only found in black, chestnut, and gray horses, we also found this allele in brown, dark bay, bay, and white horses. These results indicated that MC1R and ASIP may synergistically affect the levels of melanin in equine coat colors and that additional genes are likely involved in regulating coat colors, especially for white and gray colors. Our research provides new data for further studies on the synergetic actions of MC1R and ASIP in coat color of horses.
Publication Date: 2019-02-21 PubMed ID: 30785190PubMed Central: PMC6447268DOI: 10.1093/jas/skz071Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research study explores how the genotypes of two genes, melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP), influence the coat color of horses. The study established a correlation between these genotypes and the various shades from dark to light in horse coats.

Methodology and Findings

  • The researchers obtained and analyzed the genotypes for MC1R and ASIP in a sample of 709 horses from 15 different breeds.
  • The frequencies of the EEEE genotype at MC1R were found to decrease as the coats moved from dark colors like black (64.5%) to lighter colors such as bay (16.5%) and chestnut (0%).
  • Conversely, the AAAA genotype frequency at ASIP increased as coat colors lightened, with no instances in black horses but 83.0% prevalence in bay horses.
  • Different advantageous genotype combinations were found for each color, indicating a synergistic action of MC1R and ASIP.

Comparison with Previous Studies

  • This study contradicts some aspects of previous research by demonstrating that the AaAa allele was also found in brown, dark bay, bay, and white horses, not just black, chestnut, and gray horses as was previously believed.

Significance and Possibility of More Influencing Genes

  • The χ2 test revealed that the phenotypes of horse coat colors have a significant correlation with the genotypes of MC1R and ASIP.
  • The research points to the likelihood of more genes that are involved in the regulation of coat colors, especially for shades of white and gray.

Conclusion

  • The study concludes by affirming the relationship between MC1R and ASIP and their combined influence on the coat color of horses, paving the way for further research into this phenomenon.

Cite This Article

APA
Shang S, Yu Y, Zhao Y, Dang W, Zhang J, Qin X, Irwin DM, Wang Q, Liu F, Wang Z, Zhang S, Wang Z. (2019). Synergy between MC1R and ASIP for coat color in horses (Equus caballus)1. J Anim Sci, 97(4), 1578-1585. https://doi.org/10.1093/jas/skz071

Publication

ISSN: 1525-3163
NlmUniqueID: 8003002
Country: United States
Language: English
Volume: 97
Issue: 4
Pages: 1578-1585

Researcher Affiliations

Shang, Songyang
  • Institute of Equine Sciences, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Yu, Yan
  • Institute of Equine Sciences, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Zhao, Yuxin
  • Institute of Equine Sciences, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Dang, Wanyi
  • Institute of Equine Sciences, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Zhang, Junpeng
  • Institute of Equine Sciences, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Qin, Xia
  • Institute of Equine Sciences, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Irwin, David M
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Wang, Qin
  • Chinese Academy of Inspection and Quarantine, Beijing, China.
Liu, Fei
  • Shenyang Institute of Animal Husbandry and Veterinary Science, Shenyang, China.
Wang, Zhenshan
  • College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China.
Zhang, Shuyi
  • Institute of Equine Sciences, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Wang, Zhe
  • Institute of Equine Sciences, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.

MeSH Terms

  • Agouti Signaling Protein / genetics
  • Alleles
  • Animals
  • Breeding
  • Color
  • Female
  • Genetic Variation
  • Genotype
  • Horses / genetics
  • Horses / physiology
  • Male
  • Phenotype
  • Receptor, Melanocortin, Type 1 / genetics

References

This article includes 29 references
  1. Almathen F, Elbir H, Bahbahani H, Mwacharo J, Hanotte O. Polymorphisms in MC1R and ASIP genes are associated with coat colour variation in the Arabian camel. J. Heredity 1:7.
    pmc: PMC6108395pubmed: 29893870doi: 10.1093/jhered/esy024google scholar: lookup
  2. Campagna L, Repenning M, Silveira L F, Fontana C S, Tubaro P L, Lovette I J. Repeated divergent selection on pigmentation genes in a rapid finch radiation. Sci. Adv. 3:e1602404.
    pmc: PMC5443641pubmed: 28560331doi: 10.1126/sciadv.1602404google scholar: lookup
  3. Candille S I, Kaelin C B, Cattanach B M, Yu B, Thompson D A, Nix M A, Kerns J A, Schmutz S M, Millhauser G L, Barsh G S. A defensin mutation causes black coat color in domestic dogs. Science 318:1418–1423.
    pmc: PMC2906624pubmed: 17947548doi: 10.1126/science.1147880google scholar: lookup
  4. Chen S, Zhu B, Yin C, Liu W, Han C, Chen B, Liu T, Li X, Chen X, Li C. Palmitoylation-dependent activation of MC1R prevents melanomagenesis. Nature 549:399–403.
    pmc: PMC5902815pubmed: 28869973doi: 10.1038/nature23887google scholar: lookup
  5. Cone R D. Studies on the physiological functions of the melanocortin system. Endocr. Rev. 27:736–749.
    pubmed: 17077189doi: 10.1210/er.2006-0034google scholar: lookup
  6. Cox D R, Lewis P A W. The statistical analysis of series of events. .
  7. Dreger D L, Schmutz S M. A new mutation in MC1R explains a coat color phenotype in 2 “old” breeds: saluki and Afghan hound. J. Hered. 101:644–649.
    pubmed: 20525767doi: 10.1093/jhered/esq061google scholar: lookup
  8. Haase B, Brooks S A, Schlumbaum A, Azor P J, Bailey E, Alaeddine F, Mevissen M, Burger D, Poncet P A, Rieder S. Allelic heterogeneity at the equine KIT locus in dominant white (W) horses. PLoS Genet. 3:e195.
  9. Hauswirth R, Haase B, Blatter M, Brooks S A, Burger D, Drögemüller C, Gerber V, Henke D, Janda J, Jude R. Mutations in MITF and PAX3 cause “splashed white” and other white spotting phenotypes in horses. PLoS Genet. 8:e1002653.
  10. Hauswirth R, Jude R, Haase B, Bellone R R, Archer S, Holl H, Brooks S A, Tozaki T, Penedo M C, Rieder S. Novel variants in the KIT and PAX3 genes in horses with white-spotted coat colour phenotypes. Anim. Genet. 44:763–765.
    pubmed: 23659293doi: 10.1111/age.12057google scholar: lookup
  11. Healy E, Jordan S A, Budd P S, Suffolk R, Rees J L, Jackson I J. Functional variation of MC1R alleles from red-haired individuals. Hum. Mol. Genet. 10:2397–2402.
    pubmed: 11689486doi: 10.1093/hmg/10.21.2397google scholar: lookup
  12. Hoekstra H E, Hirschmann R J, Bundey R A, Insel P A, Crossland J P. A single amino acid mutation contributes to adaptive beach mouse color pattern. Science 313:101–104.
    pubmed: 16825572doi: 10.1126/science.1126121google scholar: lookup
  13. Holl H, Brooks S, Bailey E. De novo mutation of KIT discovered as a result of a non‐hereditary white coat colour pattern. Anim. Genetics 41:196–198.
  14. Jackson I J. Molecular and developmental genetics of mouse coat color. Annu. Rev. Genet. 28:189–217.
  15. Krajewski G, Matthews D. Analyzing linguistic data: a practical introduction to statistics using R. J. Child Lang. 37:465–470.
  16. Lalitha S. Primer premier 5. Biotech. Softw. Internet Rep.: Comput. Softw. J. Sci. 1:270–272.
    doi: 10.1089/152791600459894google scholar: lookup
  17. Lu D, Willard D, Patel I R, Kadwell S, Overton L, Kost T, Luther M, Chen W, Woychik R P, Wilkison W O. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371:799–802.
    pubmed: 7935841doi: 10.1038/371799a0google scholar: lookup
  18. Ludwig A, Pruvost M, Reissmann M, Benecke N, Brockmann G A, Castaños P, Cieslak M, Lippold S, Llorente L, Malaspinas A S. Coat color variation at the beginning of horse domestication. Science 324:485.
    pmc: PMC5102060pubmed: 19390039doi: 10.1126/science.1172750google scholar: lookup
  19. Marklund L, Moller M J, Sandberg K, Andersson L. A missense mutation in the gene for melanocyte-stimulating hormone receptor (MC1R) is associated with the chestnut coat color in horses. Mamm. Genome 7:895–899.
    pubmed: 8995760doi: 10.1007/s003359900264google scholar: lookup
  20. Metallinos D L, Bowling A T, Rine J. A missense mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome: an equine version of hirschsprung disease. Mamm. Genome 9:426–431.
    pubmed: 9585428doi: 10.1007/s003359900790google scholar: lookup
  21. Neves A P, Schwengber E B, Albrecht F F, Isola J V, van der Linden L D S. Beyond fifty shades: the genetics of horse colors. Trends Adv Vet Genet. IntechOpen .
    doi: 10.5772/65848google scholar: lookup
  22. Rieder S. Molecular tests for coat colours in horses. J. Anim. Breed. Genet. 126:415–424.
  23. Rieder S, Taourit S, Mariat D, Langlois B, Guérin G. Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus). Mamm. Genome 12:450–455.
    pubmed: 11353392doi: 10.1007/s003350020017google scholar: lookup
  24. Römpler H, Rohland N, Lalueza-Fox C, Willerslev E, Kuznetsova T, Rabeder G, Bertranpetit J, Schöneberg T, Hofreiter M. Nuclear gene indicates coat-color polymorphism in mammoths. Science 313:62.
    pubmed: 16825562doi: 10.1126/science.1128994google scholar: lookup
  25. Rosengren Pielberg G, Golovko A, Sundström E, Curik I, Lennartsson J, Seltenhammer M H, Druml T, Binns M, Fitzsimmons C, Lindgren G. A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse. Nat. Genet. 40:1004–1009.
    pubmed: 18641652doi: 10.1038/ng.185google scholar: lookup
  26. Sakamoto T, Fawcett J A, Innan H. Evaluating the potential roles of the gray and extension loci in the coat coloration of thoroughbred racing horses. J. Equine Sci. 28:61–65.
    pmc: PMC5506451pubmed: 28721125doi: 10.1294/jes.28.61google scholar: lookup
  27. Sponenberg D P, Bellone R. Equine color genetics. .
  28. Suzuki I, Cone R D, Im S, Nordlund J, Abdel-Malek Z A. Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis. Endocrinology 137:1627–1633.
    pubmed: 8612494doi: 10.1210/endo.137.5.8612494google scholar: lookup
  29. Våge D I, Nieminen M, Anderson D G, Røed K H. Two missense mutations in melanocortin 1 receptor (MC1R) are strongly associated with dark ventral coat color in reindeer (Rangifer tarandus). Anim. Genetics 45:750–753.
    pubmed: 25039753doi: 10.1111/age.12187google scholar: lookup

Citations

This article has been cited 11 times.
  1. An T, Dugarjaviin M. Differential Expression and Analysis of TBX3 Gene in Skin Tissues of Dun Mongolian Horses with and Without Bider Markings. Animals (Basel) 2026 Jan 18;16(2).
    doi: 10.3390/ani16020297pubmed: 41594486google scholar: lookup
  2. Li X, Han B, Tian D, Liu D, Ma W, Bao G, Wang L, Pei Q, Zhang Z, Zhao K. Revealing the genetic basis of coat color in Tibetan sheep through selective sweep and transcriptomic analyses. Front Vet Sci 2025;12:1711294.
    doi: 10.3389/fvets.2025.1711294pubmed: 41368031google scholar: lookup
  3. Asti V, Summer A, Ablondi M, Sartori C, Giontella A, Pilastro V, Mecocci S, Cappelli K, Mancin E, Oian A, Mantovani R, Capomaccio S, Sabbioni A. Selection signatures and inbreeding: exploring genetic diversity in five native horse breeds. BMC Vet Res 2025 May 16;21(1):346.
    doi: 10.1186/s12917-025-04794-wpubmed: 40380299google scholar: lookup
  4. Liu X, Peng Y, Zhang X, Wang X, Chen W, Kou X, Liang H, Ren W, Khan MZ, Wang C. Coloration in Equine: Overview of Candidate Genes Associated with Coat Color Phenotypes. Animals (Basel) 2024 Jun 17;14(12).
    doi: 10.3390/ani14121802pubmed: 38929421google scholar: lookup
  5. Yin Z, Hao S, Zhao Y, Li J, Cui Y, Ge Y, Pang Q. Skin proteomic screening and functional analysis of differential proteins associated with coat color in sheep (Ovis aries). Anim Biosci 2024 Sep;37(9):1503-1516.
    doi: 10.5713/ab.24.0014pubmed: 38754850google scholar: lookup
  6. Mura MC, Carcangiu V, Cosso G, Columbano N, Sanna Passino E, Luridiana S. Discrepancies between Genetic and Visual Coat Color Assignment in Sarcidano Horse. Animals (Basel) 2024 Feb 6;14(4).
    doi: 10.3390/ani14040543pubmed: 38396512google scholar: lookup
  7. Zheng H, Xiong SY, Xiao SJ, Zhang ZK, Tu JM, Cui DS, Yu NB, Huang ZY, Li LY, Guo YM. Association between MC1R gene and coat color segregation in Shanxia long black pig and Lulai black pig. BMC Genom Data 2023 Nov 30;24(1):74.
    doi: 10.1186/s12863-023-01161-2pubmed: 38036989google scholar: lookup
  8. Cosso G, Carcangiu V, Luridiana S, Fiori S, Columbano N, Masala G, Careddu GM, Sanna Passino E, Mura MC. Characterization of the Sarcidano Horse Coat Color Genes. Animals (Basel) 2022 Oct 5;12(19).
    doi: 10.3390/ani12192677pubmed: 36230420google scholar: lookup
  9. Jia X, Ding P, Chen S, Zhao S, Wang J, Lai S. Analysis of MC1R, MITF, TYR, TYRP1, and MLPH Genes Polymorphism in Four Rabbit Breeds with Different Coat Colors. Animals (Basel) 2021 Jan 5;11(1).
    doi: 10.3390/ani11010081pubmed: 33466315google scholar: lookup
  10. Corbin LJ, Pope J, Sanson J, Antczak DF, Miller D, Sadeghi R, Brooks SA. An Independent Locus Upstream of ASIP Controls Variation in the Shade of the Bay Coat Colour in Horses. Genes (Basel) 2020 May 30;11(6).
    doi: 10.3390/genes11060606pubmed: 32486210google scholar: lookup
  11. Huang X, Otecko NO, Peng M, Weng Z, Li W, Chen J, Zhong M, Zhong F, Jin S, Geng Z, Luo W, He D, Ma C, Han J, Ommeh SC, Zhang Y, Zhang X, Du B. Genome-wide genetic structure and selection signatures for color in 10 traditional Chinese yellow-feathered chicken breeds. BMC Genomics 2020 Apr 20;21(1):316.
    doi: 10.1186/s12864-020-6736-4pubmed: 32312230google scholar: lookup