Abstract
We investigated variation in the gene encoding the agouti signaling protein (ASIP) in relation to coat color evolution in primates. We found little evidence that mutations in the coding region of ASIP have been involved in color changes among closely related primate species. Among many closely related species with differing coat color, the coding region of ASIP was identical. In two cases (Sulawesi macaque and black lion tamarin) where species with almost completely black coat color had derived point mutations in exon 4 of the ASIP coding sequence, the same mutations did not alter coloration in other mammals and so probably do not affect ASIP function. Evolutionary reconstructions of two key phenotypes that are typically related to ASIP function—transverse phaeomelanin bands on hairs and pale ventral coloration—showed that these usually evolved concurrently, suggesting that loci acting downstream of ASIP may be involved. Analysis of dN/dS ratios revealed a likely change in functional constraint on ASIP following loss of agouti-banded hairs + pale ventral coloration, particularly in catarrhine primates (humans, apes, and Old World monkeys). Together with previous results on a lack of association of coat color with MC1R variation, these results suggest that other loci probably have an important role in primate coat color evolution.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bennett DC, Lamoreux ML (2003) The color loci of mice—a genetic century. Pigment Cell Res 16, 333–344
Berryere T, Kerns J, Barsh G, Schmutz S (2005) Association of an Agouti allele with fawn or sable coat color in domestic dogs. Mamm Genome 16, 262–272
Bonilla C, Boxill L-A, McDonald SA, Williams T, Sylvester N, et al. (2005) The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans. Hum Genet 116, 402–406
Bultman SJ, Michaud EJ, Woychik RP (1992) Molecular characterization of the mouse agouti locus. Cell 71, 1195–1204
Chen Y, Duhl DMJ, Barsh GS (1996) Opposite orientations of an inverted duplication and allelic variation at the mouse agouti locus. Genetics 144, 265–277
Drögemüller C, Giese A, Martins-Wess F, Wiedemann S, Andersson L, et al. (2006) The mutation causing the black-and-tan pigmentation phenotype of Mangalitza pigs maps to the porcine ASIP locus but does not affect its coding sequence. Mamm Genome 17, 58–66
Eizirik E, Yuhki N, Johnson W, Menotti-Raymond M, Hannah S, et al. (2003) Molecular genetics and evolution of melanism in the cat family. Curr Biol 13, 448–453
Girardot M, Martin J, Guibert S, Leveziel H, Julien R, et al. (2005) Widespread expression of the bovine Agouti gene results from at least three alternative promoters. Pigment Cell Res 18, 34–41
Hoekstra HE, Hirschmann RJ, Bundey RA, Insel PA, Crossland JP (2006) A single amino acid mutation contributes to adaptive beach mouse color pattern. Science 313, 101–104
Jackson IJ (1997) Homologous pigmentation mutations in human, mouse and other model organisms. Hum Mol Genet 6, 1613–1624
Kanetsky PA, Swoyer J, Panossian S, Homes R, Guerry D, et al. (2002) A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Am J Hum Genet 70, 770–775
Kerns J, Olivier M, Lust G, Barsh G (2004) Characterization of the dog Agouti gene and identification of a nonagouti mutation in German Shepherd Dogs. Mamm Genome 15, 798–808
Kiefer LL, Ittoop ORR, Bunce K, Truesdale AT, Willard DH, et al. (1997) Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors. Biochemistry 36, 2084–2090
Kiefer LL, Veal JM, Mountjoy KG, Wilkison WO (1998) Melanocortin receptor binding determinants in the agouti protein. Biochemistry 37, 991–997
Krude H, Biebermann H, Luck W, Horn R, Brabant G, et al. (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19, 155–157
Kuramoto T, Nomoto T, Sugimura T, Ushijima T (2001) Cloning of the rat agouti gene and identification of the rat nonagouti mutation. Mamm Genome 12, 469–471
Kwon H, Bultman S, Löffler C, Chen W-J, Furdon P, et al. (1994) Molecular structure and chromosomal mapping of the human homolog of the agouti gene. Proc Natl Acad Sci USA 91, 9760–9764
McNulty JC, Jackson PJ, Thompson DA, Chai B, Gantz I, et al. (2005) Structures of the Agouti signaling protein. J Mol Biol 346, 1059–1070
Mundy NI, Kelly J (2001) Phylogeny of lion tamarins (Leontopithecus) based on interphotoreceptor binding protein intron 1 sequences. Am J Primatol 54, 33–40
Mundy NI, Kelly J (2003) Evolution of a pigmentation gene, the melanocortin-1 receptor, in primates. Am J Phys Anthropol 121, 67–80
Nachman MW, Hoekstra HE, D’Agostino SL (2003) The genetic basis of adaptive melanism in pocket mice. Proc Natl Acad Sci USA 100, 5268–5273
Nakayama K, Ishida T (2006) Alu-mediated 100-kb deletion in the primate genome: the loss of the agouti signaling protein gene in the lesser apes. Genome Res 16, 485–490
Perry WL, Nakamura T, Swing DA, Secrest L, Eagleson B, et al. (1996) Coupled site-directed mutagenesis/transgenesis identifies important functional domains of the mouse agouti protein. Genetics 144, 255–264
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, 450–455
Ritland K, Newton C, Marshall HD (2001) Inheritance and population structure of the white-phased “Kermode” black bear. Curr Biol 11, 1468–1472
Römpler H, Rohland N, Lalueza-Fox C, Willerslev E, Kuznetsova T, et al. (2006) Nuclear gene indicates coat-color polymorphism in mammoths. Science 313, 62
Siracusa LD (1994) The agouti gene: turned on to yellow. Trends Genet 10, 423–428
Tota MR, Smith TS, Mao C, MacNeil T, Mosley RT, et al. (1999) Molecular interaction of agouti protein and agouti-related protein with human melanocortin receptors. Biochemistry 38, 897–904
Våge DI, Lu D, Klungland H, Lien S, Adalsteinsson S, et al. (1997) A non-epistatic interaction of agouti and extension in the fox, Vulpes vulpes. Nat Genet 15, 311–315
Voisey J, Gomez-Cabrera MdC, Smit DJ, Leonard JH, Sturm RA, et al. (2006) A polymorphism in the agouti signaling protein (ASIP) is associated with decreased levels of mRNA. Pigment Cell Res 19, 226–231
Vrieling H, Duhl D, Millar S, Miller K, Barsh G (1994) Differences in dorsal and ventral pigmentation result from regional expression of the mouse agouti gene. Proc Natl Acad Sci USA 91, 5667–5671
Wilson BD, Ollmann MM, Kang L, Stoffel M, Bell GI, et al. (1995) Structure and function of ASP, the human homolog of the mouse agouti gene. Hum Mol Genet 4, 223–230
Yang Z (1997) PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 13, 555–556
Yang Z, Bielawski JP (2000) Statistical methods for detecting molecular adaptation. Trends Ecol Evol 15, 496–503
Acknowledgments
The authors thank Andrew Kitchener, Jim Dietz, Alcides Pissinatti, Nancy Caine, Anna Feistner, Mike Bruford, Oliver Ryder, the National Museums of Scotland, the Jersey Wildlife Preservation Trust, the Institute of Zoology, and the Center for Reproduction of Endangered Species for providing samples. Brenda Bradley and two anonymous reviewers provided helpful comments on the manuscript. This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Leverhulme Trust.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mundy, N.I., Kelly, J. Investigation of the role of the agouti signaling protein gene (ASIP) in coat color evolution in primates. Mamm Genome 17, 1205–1213 (2006). https://doi.org/10.1007/s00335-006-0056-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00335-006-0056-0