title: A Val85Met mutation in melanocortin-1 receptor is associated with reductions in eumelanic pigmentation and cell surface expression in domestic rock pigeons (Columba livia).
abstract: Variation in the melanocortin-1 receptor (Mc1r) is associated with pigmentation diversity in wild and domesticated populations of vertebrates, including several species of birds. Among domestic bird species, pigmentation variation in the rock pigeon (Columbalivia) is particularly diverse. To determine the potential contribution of Mc1r variants to pigment diversity in pigeons, we sequenced Mc1r in a wide range of pigeon breeds and identified several single nucleotide polymorphisms, including a variant that codes for an amino acid substitution (Val85Met). In contrast to the association between Val85Met and eumelanism in other avian species, this change was associated with pheomelanism in pigeons. In vitro cAMP accumulation and protein expression assays revealed that Val85Met leads to decreased receptor function and reduced cell surface expression of the mutant protein. The reduced in vitro function is consistent with the observed association with reduced eumelanic pigmentation. Comparative genetic and cellular studies provide important insights about the range of mechanisms underlying diversity among vertebrates, including different phenotypic associations with similar mutations in different species.
authors: Department of Biology, University of Utah, Salt Lake City, Utah, United States of America.
authors: Michael W
authors: MW
authors: Guernsey
authors: Lars
authors: L
authors: Ritscher
authors: Matthew A
authors: MA
authors: Miller
authors: Daniel A
authors: DA
authors: Smith
authors: Torsten
authors: T
authors: Schöneberg
authors: Michael D
authors: MD
authors: Shapiro
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism*; D010856:Columbidae / Q000235:genetics*; D005241:Feathers / Q000502:physiology; D006239:Haplotypes / Q000235:genetics; D008543:Melanins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D010858:Pigmentation / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D008543:Melanins; D044102:Receptor, Melanocortin, Type 1; C018362:pheomelanin; C041877:eumelanin
references: Evolution. 2007 May;61(5):995-1016
references: 17492956
references: Science. 2004 Mar 19;303(5665):1870-3
references: 15031505
references: Am Nat. 2009 Aug;174(2):244-54
references: 19489704
references: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2113-7
references: 20080544
references: J Hered. 2007 Jul-Aug;98(4):287-92
references: 17602182
references: Curr Biol. 2013 Apr 22;23(8):R302-3
references: 23618660
references: Philos Trans R Soc Lond B Biol Sci. 2010 Aug 27;365(1552):2439-50
references: 20643733
references: FASEB J. 2012 Aug;26(8):3273-81
references: 22611087
references: Science. 2013 Mar 1;339(6123):1063-7
references: 23371554
references: Trends Genet. 2003 Nov;19(11):585-8
references: 14585605
references: Curr Biol. 2012 Feb 21;22(4):302-8
references: 22264611
references: Cell Mol Biol (Noisy-le-grand). 2006 May 30;52(2):39-46
references: 16914085
references: Anim Genet. 2006 Jun;37(3):287-9
references: 16734695
references: Science. 2006 Jul 7;313(5783):101-4
references: 16825572
references: Hum Mutat. 1998;12(3):196-205
references: 9711877
references: Biochim Biophys Acta. 1996 Aug 14;1308(2):164-8
references: 8764834
references: Proc Natl Acad Sci U S A. 2009 Jun 16;106 Suppl 1:9971-8
references: 19528637
references: Heredity (Edinb). 2006 Sep;97(3):222-34
references: 16823403
references: Curr Biol. 2001 Apr 17;11(8):550-7
references: 11369199
references: J Med Genet. 2005 Jul;42(7):583-7
references: 15994880
references: Eur J Biochem. 2002 Dec;269(24):6133-41
references: 12473109
references: Anim Genet. 2003 Aug;34(4):241-8
references: 12873211
references: Eur J Biochem. 2003 Apr;270(7):1441-9
references: 12653999
references: J Hered. 2012 May-Jun;103(3):315-21
references: 22504110
references: Proc Biol Sci. 2005 Aug 22;272(1573):1633-40
references: 16087416
references: Genetica. 2002 Nov;116(2-3):311-27
references: 12555787
references: PLoS Biol. 2007 Sep;5(9):e219
references: 17696646
references: J Evol Biol. 2011 Sep;24(9):2055-63
references: 21696477
references: Anim Genet. 2013 Apr;44(2):214-6
references: 22591010
references: J Hered. 2007 Sep-Oct;98(6):567-74
references: 17646275
references: Poult Sci. 2010 Aug;89(8):1599-602
references: 20634512
references: PLoS Genet. 2009 Jan;5(1):e1000326
references: 19119422
references: Evolution. 2004 Aug;58(8):1794-808
references: 15446431
references: Gene. 2013 Jan 25;513(2):282-6
references: 23116942
references: Cold Spring Harb Symp Quant Biol. 2009;74:319-25
references: 20375320
references: BMC Evol Biol. 2008 Sep 12;8:249
references: 18789136
references: Mol Biol Evol. 2009 Jan;26(1):35-45
references: 18832078