Abstract
Agouti is a common pigmentation phenotype in mammals including primates. Mutations in the agouti signaling protein gene (ASIP) are known to result in non-agouti black hairs in laboratory mice. It is still unclear whether sequence variation in ASIP is linked with the agouti/non-agouti phenotypes in macaques (Genus Macaca). To address this issue, we have determined and compared nucleotide sequences of protein coding region of ASIP in 18 macaque species and have identified 16 different sequences of the ASIP. Macaca nemestrina, which showed yellow agouti hairs, shared an identical amino acid sequence of ASIP with several non-agouti species. No sequence changes were found in functionally important sites of ASIP in the macaques showing non-agouti dark hair color. These results indicated that the variation in the protein coding region of ASIP did not explain the non-agouti dark coat color in the macaques. Upstream regulatory regions of ASIP and other genes participating in pigmentation system remain to be investigated for the hair color variation in the macaques.
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Bonilla C, Boxill LA, Donald SA, Williams T, Sylvester N, Parra EJ, Dios S, Norton HL, Shriver MD, Kittles RA (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
Drögemüller C, Giese A, Martins-Wess F, Wiedemann S, Andersson L, Brenig B, Fries R, Leeb T (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 WE, Menotti-Raymond M, Hannah SS, O’Brien SJ (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, Oulmouden A (2005) Widespread expression of the bovine agouti gene results from at least three alternative promoters. Pigment Cell Res 18:34–41
Hamada Y, Watanabe T, Takenaka O, Suryobroto B, Kawamoto Y (1988) Morphological studies on the Sulawesi macaques I: phyletic analysis of body color. Primates 29:65–80
Inagaki H (1996) Some hair characteristics of Macaca monkeys and an attempt to group them based on those features. In: Shotake T, Wada K (eds) Variations in the Asian Macaques. Tokai University Press, Tokyo, Japan, pp 89–96
Kanetsky PA, Swoyer J, Panossian S, Holmes R, Guerry D, Rebbeck TR (2002) A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Am J Hum Genet 70:770–775
Kerns JA, Newton J, Berryere TG, Rubin EM, Cheng JF, Schmutz SM, Barsh GS (2004) Characterization of the dog agouti gene and a nonagouti mutation in German Shepherd dogs. Mamm Genome 15:798–808
Kiefer LL, Ittoop OR, Bunce K, Truesdale AT, Willard DH, Nichols JS, Blanchard SG, Mountjoy K, Chen WJ, Wilkison WO (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
Kingsley EP, Manceau M, Wiley CD, Hoekstra HE (2009) Melanism in Peromyscus is caused by independent mutations in agouti. PLoS One 4:e6435
Kumar P, Henikoff S, Ng PC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4:1073–1081
Kumar S, Tamura K, Nei M (2004) MEGA3: Integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5:150–163
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
McNulty JC, Jackson PJ, Thompson DA, Chai B, Gantz I, Barsh GS, Dawson PE, Millhauser GL (2005) Structures of the agouti signaling protein. J Mol Biol 346:1059–1070
Mundy NI, Kelly J (2003) Evolution of a pigmentation gene, the melanocortin-1 receptor, in primates. Am J Phys Anthropol 121:67–80
Mundy NI, Kelly J (2006) Investigation of the role of the agouti signaling protein gene (ASIP) in coat color evolution in primates. Mamm Genome 17:1205–1213
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
Nakayama K, Shotake T, Takeneka O, Ishida T (2008) Variation in the Melanocortin 1 receptor gene in the macaques. Am J Primatol 70:778–785
Perry WL, Hustad CM, Swing DA, Jenkins NA, Copeland NG (1995) A transgenic mouse assay for agouti protein activity. Genetics 140:267–274
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
Robbins LS, Nadeau JH, Johnson KR, Kelly MA, Roselli-Rehfuss L, Baack E, Mountjoy KG, Cone RD (1993) Pigmentation phenotypes of variant extension locus alleles result from point mutations that later MSH receptor function. Cell 72:827–834
Rowe N (1996) The Pictorial Guide to the Living Primates. Pogonias Press, Charlestown, USA
Sturm RA (2006) A golden age of human pigmentation genetics. Trends Genet 22:464–468
Tota MR, Smith TS, Mao C, MacNeil T, Mosley RT, Van der Ploeg LH, Fong TM (1999) Molecular interaction of agouti protein and agouti-related protein with human melanocortin receptors. Biochemistry 38:897–904
Våge DI, Klungland H, Lu D, Cone RD (1999) Molecular and pharmacological characterization of dominant black coat colour in sheep. Mamm Genome 10:39–43
Våge DI, Lu D, Klungland H, Lien S, Adalsteinsson S, Cone RD (1997) A non-epistatic interaction of agouti and extension in the fox, Vulpes vulpes. Nat Genet 15:311–315
Vrieling H, Duhl DM, Millar SE, Miller KA, Barsh GS (1994) Differences in dorsal and ventral pigmentation result from regional expression of the mouse agouti gene. Proc Natl Acad Sci USA 91:5667–5671
Acknowledgements
This study was partly supported by Japan Society for Promotion of Science, Ministry of Education, Culture, Sports, Science and Technology, Japan and The University of Tokyo. This study constitutes a part of the doctoral thesis of Kazuhiro Nakayama submitted to The University of Tokyo, Japan. We confirmed that the experimental design was approved by animal care and use of committee for the University of Tokyo and applicable national laws.
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Osamu Takeneka: Deceased 3 March 2005
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Nakayama, K., Shotake, T., Takeneka, O. et al. Variations in the Coding Region of the Agouti Signaling Protein Gene Do Not Explain Agouti/Non-agouti Phenotypes in Macaques. J Mammal Evol 17, 211–214 (2010). https://doi.org/10.1007/s10914-010-9137-7
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DOI: https://doi.org/10.1007/s10914-010-9137-7