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Journal of Mammalian Evolution

, Volume 20, Issue 3, pp 263–270 | Cite as

Coat Color Variation and Pigmentation Gene Expression in Rhesus Macaques (Macaca mulatta)

  • Brenda J. BradleyEmail author
  • Melissa S. Gerald
  • Anja Widdig
  • Nicholas I. Mundy
Original Paper

Abstract

Light-dark coat color variation is a common aspect of color diversity within and across mammalian taxa. This variation in pelage brightness is associated with aspects of evolutionary ecology, particularly for primates, but little is known about the genetic mechanisms underlying light-dark differences in pelage pigmentation. Previous work, focusing particularly on macaques (Genus Macaca), has found no clear relationship between color variation and coding sequences of key pigmentation genes. This suggests that other loci and/or gene regulatory differences underlie this variation and raises the question of how patterns of gene expression differ in light verses dark hair follicles. Here, we examine relative expression levels of pigmentation genes in hair follicles from free-ranging rhesus macaques (Macaca mulatta) showing stark light-dark coat color variation. We quantified the brightness (reflectance) of plucked hair tufts using a spectrophotometer. We extracted RNA from the follicles and used quantitative RT-PCR to measure the relative amounts of gene product (mRNA) for seven candidate pigmentation genes (MITF, MC1R, MGRN1, ATRN, SLC24A5, TYRP1, and DCT). Expression values were normalized with the house-keeping gene ACTB. All candidate genes were expressed at similar levels in dark, intermediate, and light hair, and thus, light-dark variation in macaque coat color is unlikely to be due to differences in the expression of these key pigmentation genes. This study represents the first examination of gene expression and natural color variation in a non-human primate population. Our results indicate that even in a system, like pigmentation, where a candidate-gene approach is promising, identifying important intra-specific gene regulatory differences remains challenging.

Keywords

Melanin Pelage Coloration Coat color Melanocyte Gene expression 

Notes

Acknowledgments

We are grateful to Jenny Pastorini for help with primer design and PCR product verification, to the Caribbean Primate Research Center for support to conduct this research, to Edgar Davíla and Julio Resto for maintaining a daily census of the Cayo Santiago population, and the staff of Cayo Santiago for preserving the well-being of the monkeys of Cayo Santiago. We thank James Higham for the photo used in Fig. 1a. The rhesus macaque population of Cayo Santiago is supported by the University of Puerto Rico, Medical Sciences Campus and by the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) (NCRR grant P40RR003640 award to the Caribbean Primate Research Center). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of NCRR or NIH. All research procedures were approved by the CPRC and the Institutional Animal Care and Use Committee (IACUC) of the University of Puerto Rico (protocol number Widdig 4060105). The export of hair samples was approved by the FWS (Cites Export permission # 06US112079/9, Cites Import permission # E-1082/06). This work was funded by the UK Natural Environment Research Council, the UK Biotechnology and Biological Sciences Research Council, The Leverhulme Trust, the German Research Foundation, and Yale University.

References

  1. Anderson TM, vonHoldt BM, Candille SI, Musiani M, Greco C, Stahler DR, Smith DW, Padhukasahasram B, Randi E, Leonard JA, Bustamante CD, Ostrander EA, Tang, Wayne RK, Barsh GS (2009) Molecular and evolutionary history of melanism in North American gray wolves. Science 323:1339-1343CrossRefPubMedGoogle Scholar
  2. Blume-Peytavi U, Tosti A, Whiting D, Trueb R (2008) Hair Growth and Disorders. The Johns Hopkins University Press, BaltimoreCrossRefGoogle Scholar
  3. Bradley BJ, Lawler RR (2011) Linking genotypes, phenotypes, and fitness in wild primate populations. Evol Anthropol 20:104–119CrossRefPubMedGoogle Scholar
  4. Bradley BJ, Mundy NI (2008) The primate palette: the evolution of primate coloration. Evol Anthropol 17:97–111CrossRefGoogle Scholar
  5. Bradley BJ, Pastorini J, Mundy NI (2005) Successful retrieval of mRNA from hair follicles stored at room temperature: implications for studying gene expression in wild mammals. Mol Ecol Notes 5:961–964CrossRefGoogle Scholar
  6. Bradley BJ, Pedersen A, Mundy NI (2009) Blue eyes in lemurs and humans: same phenotype, different genetic mechanism. Am J Phys Anthropol 139:269–273CrossRefGoogle Scholar
  7. Burtt EH, Ichida JM (2004) Gloger’s rule, feather-degrading bacteria, and color variation among song sparrows. The Condor 106:681–686CrossRefGoogle Scholar
  8. Bustin S, Benes V, Nolan T, Pfaffl M (2005) Quantitative real-time RT-PCR—a perspective. J Mol Endocrinol 34:597–601CrossRefPubMedGoogle Scholar
  9. Candille SI, Kaelin CB, Cattanach BM, Yu B, Thompson DA, Nix MA, Kerns JA, Schmutz SM, Millhauser GL, Barsh GS (2007) A beta-defensin mutation causes black coat color in domestic dogs. Science 318:1418–1423CrossRefPubMedGoogle Scholar
  10. Caro T (2005) The adaptive significance of coloration in mammals. BioScience 55:125–136CrossRefGoogle Scholar
  11. Caro T (2009) Contrasting coloration in terrestrial mammals. Phil Trans R Soc B 364:537–548CrossRefPubMedGoogle Scholar
  12. Endler JA (1990) On the measurement and classification of colour in studies of animal colour patterns. Biol J Linn Soc 41:315–352CrossRefGoogle Scholar
  13. Gerald MS (2003) How color can guide the primate world. In: Jones CB (ed) Sexual Selection and Reproductive Competition in Primates: New Perspectives and Directions. American Society of Primatologists, Norman, Oklahoma, pp 141–172Google Scholar
  14. Gloger CL (1833) Das Abändern der Vögel durch Einfluss des Klimas. August Schulz, BreslauCrossRefGoogle Scholar
  15. Gompel N, Prud’homme B, Wittkopp PJ, Kassner VA, Carroll SB (2005) Chance caught on the wing: cis-regulatory evolution and the origin of pigment patterns in Drosophila. Nature 433:481–7CrossRefPubMedGoogle Scholar
  16. Gratten J, Beraldi D, Lowder BV, McRae AF, Visscher PM, Pemberton JM, Slate J (2007) Compelling evidence that a single nucleotide substitution in TYRP1 is responsible for coat-colour polymorphism in a free-living population of Soay sheep. Proc R Soc B 274:619–626CrossRefPubMedGoogle Scholar
  17. Hamada Y, Urasopon N, Hadi I, Malaivijitnond S (2006) Body size and proportions and pelage color of free-ranging Macaca mulatta from a zone of hybridization in northeastern Thailand. Int J Primatol 27:497–513CrossRefGoogle Scholar
  18. Hamada Y, Suryobroto B, Goto S, Malaivijitnond S (2008) Morphological and body color variation in Thai Macaca fascicularis fascicularis north and south of the Isthmus of Kra. Int J Primatol 29:1271–1294CrossRefGoogle Scholar
  19. Hardy MH (1992) The secret life of the hair follicle. Trends Genet 8:55–61PubMedGoogle Scholar
  20. He L, Eldridge AG, Jackson PK, Gunn TM, Barsh GS (2002) Accessory proteins for melanocortin signaling—attractin and mahogunin. Paper presented at the 5th International Melanocortin Meeting, Sunriver, OregonGoogle Scholar
  21. Hill GE, McGraw KJ (2006) Bird Coloration, vol. 2. Function and Evolution. Harvard University Press, CambridgeGoogle Scholar
  22. Hoekstra HE (2006) Genetics, development and evolution of adaptive pigmentation in vertebrates. Heredity 97:222–234CrossRefPubMedGoogle Scholar
  23. Hubbard JK, Uy JAC, Hauber ME, Hoekstra HE, Safran RJ (2010) Vertebrate pigmentation: from underlying genes to adaptive function. Trends Genet 26:231–239CrossRefPubMedGoogle Scholar
  24. Jackson IJ (1997) Homologous pigmentation mutations in human, mouse and other model organisms. Hum Mol Genet 6:1613–1624CrossRefPubMedGoogle Scholar
  25. Kamilar JM, Bradley BJ (2011) Interspecific variation in primate coat color supports Gloger’s rule. J Biogeogr 38:2270–2277CrossRefGoogle Scholar
  26. Kessler MJ, Rawlins RG, Kaufman PL (1986) The golden rhesus macaques of Cayo Santiago. In: Rawlins RG, Kessler MJ (eds) The Cayo Santiago Macaques: History, Behavior and Biology. State University of New York Press, Albany, pp 263–268Google Scholar
  27. Khouangsathiene S, Pearson C, Street S, Ferguson B, Dubay C (2008) MonkeySNP: a web portal for non-human primate single nucleotide polymorphisms. Bioinformatics 24:2645–2646CrossRefPubMedGoogle Scholar
  28. Kidson SH, Fabian BC (1981) The effect of temperature on tyrosinase activity in Himalayan mouse skin. J Exp Zool 215:91–97CrossRefPubMedGoogle Scholar
  29. Klee EW, Erdogan S, Tillmans L, Kosari F, Sun F, Wigle DA, Yang P, Aubry MC, Vasmatzis G (2009) Impact of sample acquisition and linear amplification on gene expression profiling of lung adenocarcinoma: laser capture micro-dissection cell-sampling versus bulk tissue-sampling. BMC Med Genomics 2:13CrossRefPubMedGoogle Scholar
  30. Koyabu D, Malaivijitnond S, Hamada Y (2008) Pelage color variation of Macaca arctoides and its evolutionary implications. Int J Primatol 29: 531–541CrossRefGoogle Scholar
  31. Lalueza-Fox C, Rompler H, Caramelli D, Staubert C, Catalano G, Hughes D, Rohland N, Pilli E, Longo L, Condemi S, de la Rasilla M, Fortea J, Rosas A, Stoneking M, Schöneberg T, Bertranpetit J, Hofreiter M (2007) A melanocortin 1 receptor allele suggests varying pigmentation among neanderthals. Science 318:1453–1455CrossRefPubMedGoogle Scholar
  32. Lamason RL, Mohideen M, Mest JR, Wong AC, Norton HL, Aros MC, Jurynec MJ, Mao X, Humphreville VR, Humbert JE, Sinha S, Moore JL, Jagadeeswaran P, Zhao W, Ning G, Makalowska I, McKeigue PM, O’Donnell D, Kittles R, Parra EJ, Mangini NJ, Grunwald DJ, Shriver MD, Canfield VA, Cheng KC (2005) SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310: 1782–1786CrossRefPubMedGoogle Scholar
  33. Lamoreux M, Delmas V, Larue L, Bennett D (2010) The Colors of Mice: A Model Genetic Network. Wiley Blackwell, HobokenCrossRefGoogle Scholar
  34. Levy C, Khaled M, Fisher DE (2006) MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 12:406–414CrossRefGoogle Scholar
  35. Li S, Wang C, Yu W, Zhao S, Gong Y (2012) Identification of genes related to white and black plumage formation by RNA-Seq from white and black feather bulbs in ducks. PLoS ONE 7: e36592CrossRefPubMedGoogle Scholar
  36. Lyons LA, Foe IT, Rah HC, Grahn RA (2005) Chocolate coated cats: TYRP1 mutations for brown color in domestic cats. Mammal Genome 16:356–66CrossRefGoogle Scholar
  37. Mamanova L, Coffey AJ, Scott CE, Kozarewa I, Turner EH, Kumar A, Howard E, Shendure J, Turner DJ (2010) Target-enrichment strategies for next-generation sequencing. Nat Methods 7:111–118CrossRefPubMedGoogle Scholar
  38. Manceau M, Domingues VS, Linnen CR, Rosenblum EB, Hoekstra HE (2010) Convergence in pigmentation at multiple levels: mutations, genes and function. Proc R Soc B 365:2439–2450Google Scholar
  39. Manceau M, Domingues VS, Mallarino R, Hoekstra HE (2011) The developmental role of Agouti in color pattern evolution. Science 331:1062–1065CrossRefPubMedGoogle Scholar
  40. Martínez-Arias R, Comas D, Andrés A, Abelló M-T, Domingo-Roura X, Bertranpetit J (2000) The Tyrosinase gene in gorillas and the albinism of ‘Snowflake’. Pigment Cell Res 13:467–470CrossRefPubMedGoogle Scholar
  41. Mikkelsen TS, Hillier LW, Eichler EE, Zody MC, Jaffe DB, Yang S-P, Enard W, Hellmann I, Lindblad-Toh K, Altheide TK, Archidiacono N, Bork P, Butler J, Chang JL, Cheng Z, Chinwalla AT, de Jong P, Delehaunty KD, Fronick CC, Fulton LL, Gilad Y, Glusman G, Gnerre S, Graves TA, Hayakawa T, Hayden KE, Huang X, Ji H, Kent WJ, King M-C, Kulbokasl EJ, Lee MK, Liu G, Lopez-Otin C, Makova KD, Man O, Mardis ER, Mauceli E, Miner TL, Nash WE, Nelson JO, Pääbo S, Patterson NJ, Pohl CS, Pollard KS, Prüfer K, Puente XS, Reich D, Rocchi M, Rosenbloom K, Ruvolo M, Richter DJ, Schaffner SF, Smit AF, Smith SM, Suyama M, Taylor J, Torrents D, Tuzun E, Varki A, Velasco G, Ventura M, Wallis JW, Wendl MC, Wilson RK, Lander ES, Waterston RH (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437:69–87CrossRefGoogle Scholar
  42. Morgan HD, Sutherland HG, Martin DI, Whitelaw E (1999) Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23:314–318CrossRefPubMedGoogle Scholar
  43. Mundy NI (2005) A window on the genetics of evolution: MC1R and plumage coloration in birds. Proc R Soc B 272:1633–1640Google Scholar
  44. Mundy NI, Kelly J (2003) Evolution of a pigmentation gene, the melanocortin-1 receptor, in primates. Am J Phys Anthropol 121:67–80CrossRefPubMedGoogle Scholar
  45. Mundy NI, Kelly J (2006) Investigation of the role of the agouti signaling protein gene (ASIP) in coat color evolution in primates. Mammal Genome 17: 1205–1213CrossRefGoogle Scholar
  46. Nakayama K, Shotake T, Takeneka O, Ishida T (2008) Variation of the melanocortin 1 receptor gene in the macaques. Am J Primatol 70:778–785CrossRefPubMedGoogle Scholar
  47. Nakayama K, Shotake T, Takeneka O, Ishida T (2010) Variations in the coding region of the agouti signaling protein gene do not explain agouti/non-agouti phenotypes in macaques. J Mammal Evol 17:211–214CrossRefGoogle Scholar
  48. Nishimura EK, Granter SR, Fisher DE (2005) Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 307:720–724CrossRefPubMedGoogle Scholar
  49. Nordlund J, Boissy RE, Hearing V, King RA, Oetting WS (2006) The Pigmentary System: Physiology and Pathophysiology, 2nd Edition. Wiley-Blackwell, HobokenCrossRefGoogle Scholar
  50. Ortolani A, Caro TM (1996) The adaptive significance of color patterns in carnivores: phylogenetic tests of classic hypotheses. In: Gittleman JL (ed) Carnivore Behavior, Ecology, and Evolution, Comstock Press, Ithaca, pp 132–188Google Scholar
  51. Ostner J (2006) Macaques. Current Biol 16:R569–R570.CrossRefGoogle Scholar
  52. Pfaffl M (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45CrossRefPubMedGoogle Scholar
  53. Rawlins RG, Kessler MJ (1986) The Cayo Santiago Macaques. History, Behavior and Biology. State University of New York Press, AlbanyGoogle Scholar
  54. Rieder S, Taourit S, Mariat D, Langlois B, Guérin G (2001) 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 12:450–455Google Scholar
  55. Rogers GE, Powell BC (1993) Organization and expression of hair follicle genes. J Invest Dermatol 101: 50S–55SCrossRefGoogle Scholar
  56. Ross C, Regan G (2000) Allocare, predation risk, social structure and natal coat colour in anthropoid primates. Folia Primatol 71:67–76CrossRefPubMedGoogle Scholar
  57. Santana SE, Alfaro JL, Alfaro ME (2012) Adaptive evolution of facial colour patterns in Neotropical primates. Proc R Soc B. 279:2204–2211CrossRefPubMedGoogle Scholar
  58. Schmittgen T, Livak K (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protocols 3:1101–1108CrossRefGoogle Scholar
  59. Shibahara S, Yasumoto K, Amae S, Udono T, Watanabe K, Saito H, Takeda K (2000) Regulation of pigment cell-specific gene expression by MITF. Pigment Cell Res 8:98–102CrossRefGoogle Scholar
  60. Sponenberg DG (2009) Equine Color Genetics (3rd ed.). Wiley-Blackwell, AmesGoogle Scholar
  61. Steiner C, Weber JN, Hoekstra HE (2007) Adaptive variation in beach mice produced by two interacting pigmentation genes. PLoS Biology 5, e219 doi:210.1371CrossRefPubMedGoogle Scholar
  62. Steingrimsson E, Copeland N, Jenkins N (2004) Melanocytes and the microphthalmia transcription factor network. Annu Rev Genet 38:365–411CrossRefPubMedGoogle Scholar
  63. Stoner CJ, Caro TM, Graham CM (2003) Ecological and behavioral correlates of coloration in artiodactyls: systematic analyses of conventional hypotheses. Behav Ecol 14:823–840CrossRefGoogle Scholar
  64. Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, Wang X, Bodeau J, Tuch BB, Siddiqui A, Lao K, Surani MA (2009) mRNA-Seq whole-transcriptome analysis of a single cell. Nature Methods 6:377–382CrossRefPubMedGoogle Scholar
  65. Treves A (1997) Primate natal coats: a preliminary analysis of distribution and function. Am J Primatol 104:47–70Google Scholar
  66. Villano J, Ogden B, Yong P, Lood N, Sharp P (2009) Morphometrics and pelage characterization of longtailed macaques (Macaca fascicularis) from Pulau Bintan, Indonesia; Singapore; and southern Vietnam. J Am Assoc Lab Animal Science 48:727–733Google Scholar
  67. West PM, Packer C (2003) Melanin, nutrition, and the lion’s mane. Science 299:660Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Brenda J. Bradley
    • 1
    Email author
  • Melissa S. Gerald
    • 2
    • 3
  • Anja Widdig
    • 4
    • 5
  • Nicholas I. Mundy
    • 6
  1. 1.Department of AnthropologyYale UniversityNew HavenUSA
  2. 2.Department of Medicine, Medical Sciences CampusUniversity of Puerto RicoSan JuanUSA
  3. 3.Laboratory for Primate Morphology and GeneticsUniversity of Puerto Rico Medical SchoolSan JuanUSA
  4. 4.Junior Research Group on Primate Kin Selection, Department of PrimatologyMax Planck Institute for Evolutionary AnthropologyLeipzigGermany
  5. 5.Institute for BiologyUniversity of LeipzigLeipzigGermany
  6. 6.Department of ZoologyUniversity of CambridgeCambridgeUK

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