title: Testing whether macroevolution follows microevolution: are colour differences among swans (Cygnus) attributable to variation at the MCIR locus?
abstract: BACKGROUND
  The MC1R (melanocortin-1 receptor) locus underlies intraspecific variation in melanin-based dark plumage coloration in several unrelated birds with plumage polymorphisms. There is far less evidence for functional variants of MC1R being involved in interspecific variation, in which spurious genotype-phenotype associations arising through population history are a far greater problem than in intraspecific studies. We investigated the relationship between MC1R variation and plumage coloration in swans (Cygnus), which show extreme variation in melanic plumage phenotypes among species (white to black).
  
  
  RESULTS
  The two species with melanic plumage, C. atratus and C. melanocoryphus (black and black-necked swans respectively), both have amino acid changes at important functional sites in MC1R that are consistent with increased MC1R activity and melanism. Reconstruction of MC1R evolution over a newly generated independent molecular phylogeny of Cygnus and related genera shows that these putative melanizing mutations were independently derived in the two melanic lineages. However, interpretation is complicated by the fact that one of the outgroup genera, Coscoroba, also has a putative melanizing mutation at MC1R that has arisen independently but has nearly pure white plumage. Epistasis at other loci seems the most likely explanation for this discrepancy. Unexpectedly, the phylogeny shows that the genus Cygnus may not be monophyletic, with C. melanocoryphus placed as a sister group to true geese (Anser), but further data will be needed to confirm this.
  
  
  CONCLUSIONS
  Our study highlights the difficulty of extrapolating from intraspecific studies to understand the genetic basis of interspecific adaptive phenotypic evolution, even with a gene whose structure-function relationships are as well understood as MC1R as confounding variation make clear genotype/phenotype associations difficult at the macroevolutionary scale. However, the identification of substitutions in the black and black-necked swan that are known to be associated with melanic phenotypes, suggests Cygnus may be another example where there appears to be convergent evolution at MC1R. This study therefore provides a novel example where previously described intraspecific genotype/phenotype associations occur at the macroevolutionary level.
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge, UK. map50@cam.ac.uk
authors.forename: Marie A
authors.initials: MA
authors.lastname: Pointer
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Mundy
mesh_terms: D000818:Animals; D046090:Anseriformes / Q000235:genetics*; D045303:Cytochromes b / Q000235:genetics; D004247:DNA / Q000235:genetics; D019143:Evolution, Molecular; D005241:Feathers; D014644:Genetic Variation; D007527:Isoenzymes / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D016013:Likelihood Functions; D008957:Models, Genetic; D010641:Phenotype; D010802:Phylogeny; D010858:Pigmentation / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D007527:Isoenzymes; D044102:Receptor, Melanocortin, Type 1; D004247:DNA; D045303:Cytochromes b; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1
references.citation: Science. 2004 Mar 19;303(5665):1870-3
references.pmid: 15031505
references.citation: Mol Biol Evol. 2003 Oct;20(10):1675-81
references.pmid: 12885967
references.citation: Curr Biol. 2001 Sep 18;11(18):1468-72
references.pmid: 11566108
references.citation: Mol Ecol. 2003 May;12(5):1185-94
references.pmid: 12694282
references.citation: Science. 2006 Jul 7;313(5783):62
references.pmid: 16825562
references.citation: Proc Biol Sci. 2005 Aug 22;272(1573):1633-40
references.pmid: 16087416
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5268-73
references.pmid: 12704245
references.citation: Am J Phys Anthropol. 2003 May;121(1):67-80
references.pmid: 12687585
references.citation: Curr Biol. 2003 Mar 4;13(5):448-53
references.pmid: 12620197
references.citation: Mol Biol Evol. 1994 Mar;11(2):261-77
references.pmid: 8170367
references.citation: Anim Genet. 2006 Jun;37(3):287-9
references.pmid: 16734695
references.citation: Heredity (Edinb). 2006 Sep;97(3):222-34
references.pmid: 16823403
references.citation: Curr Biol. 2001 Apr 17;11(8):550-7
references.pmid: 11369199
references.citation: J Hered. 2007 Jul-Aug;98(4):287-92
references.pmid: 17602182
references.citation: Bioinformatics. 2001 Aug;17(8):754-5
references.pmid: 11524383
references.citation: Eur J Biochem. 2003 Apr;270(7):1441-9
references.pmid: 12653999
references.citation: Biochem Biophys Res Commun. 1999 Jul 5;260(2):488-91
references.pmid: 10403794
references.citation: Mol Phylogenet Evol. 2005 Oct;37(1):83-90
references.pmid: 16182151
references.citation: Cell. 1993 Mar 26;72(6):827-34
references.pmid: 8458079
references.citation: Bioinformatics. 1998;14(9):817-8
references.pmid: 9918953
references.citation: Evolution. 2004 Aug;58(8):1794-808
references.pmid: 15446431
references.citation: Proc Biol Sci. 2004 Aug 22;271(1549):1663-70
references.pmid: 15306285
references.citation: Comput Appl Biosci. 1997 Oct;13(5):555-6
references.pmid: 9367129
references.citation: Proc Biol Sci. 2007 Aug 7;274(1620):1807-13
references.pmid: 17504743
references.citation: Biochim Biophys Acta. 1996 May 2;1306(2-3):122-6
references.pmid: 8634326
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417
references.citation: Hum Mol Genet. 1997;6(10):1613-24
references.pmid: 9300652
references.citation: Science. 2006 Jul 7;313(5783):101-4
references.pmid: 16825572
references.citation: Mol Phylogenet Evol. 2002 Jun;23(3):339-56
references.pmid: 12099792
references.citation: Mol Biol Evol. 2007 Sep;24(9):2001-8
references.pmid: 17609536
references.citation: Mol Phylogenet Evol. 1994 Jun;3(2):85-91
references.pmid: 7521252