title: Positive selection drives the evolution of a major histocompatibility complex gene in an endangered Mexican salamander species complex.
abstract: Immune gene evolution can be critical to species survival in the face of infectious disease. In particular, polymorphism in the genes of the major histocompatibility complex (MHC) helps vertebrates combat novel and diverse pathogens by increasing the number of pathogen-derived proteins that can initiate the host's acquired immune response. In this study, we used a combination of presumably adaptive and neutral markers to investigate MHC evolution in populations of five salamander species within the Ambystoma velasci complex, a group consisting of 15 recently diverged species, several of which are endangered. We isolated 31 unique MHC class II β alleles from 75 total individuals from five species in this complex. MHC heterozygosity was significantly lower than expected for all five species, and we found no clear relationship between number of MHC alleles and species range, life history, or level of heterozygosity. We inferred a phylogeny representing the evolutionary history of Ambystoma MHC, with which we found signatures of positive selection on the overall gene, putative peptide-binding residues, and allelic lineages. We identified several instances of trans-species polymorphism, a hallmark of balancing selection observed in other groups of closely related species. In contrast, we did not detect comparable allelic diversity or signatures of selection on neutral loci. Additionally, we identified 17 supertypes among the 44 unique Ambystoma alleles, indicating that these sequences may encode functionally distinct MHC variants. We therefore have strong evidence that positive selection is a major evolutionary force driving patterns of MHC polymorphism in this recently radiated species complex.
authors.affiliation: Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY, USA, ket45@cornell.edu.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Tracy
authors.forename: Karen M
authors.initials: KM
authors.lastname: Kiemnec-Tyburczy
authors.forename: J Andrew
authors.initials: JA
authors.lastname: DeWoody
authors.forename: Gabriela
authors.initials: G
authors.lastname: Parra-Olea
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Zamudio
mesh_terms: D000483:Alleles; D000558:Ambystoma mexicanum / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D056727:Endangered Species; D019143:Evolution, Molecular; D008285:Major Histocompatibility Complex / Q000235:genetics*; D010802:Phylogeny; D012641:Selection, Genetic / Q000235:genetics*
references.citation: Mol Biol Evol. 2013 May;30(5):1196-205
references.pmid: 23420840
references.citation: Nature. 1993 Jul 1;364(6432):33-9
references.pmid: 8316295
references.citation: Mol Ecol. 2009 Aug;18(15):3307-15
references.pmid: 19508451
references.citation: Genetics. 2006 Mar;172(3):1411-25
references.pmid: 16387887
references.citation: Syst Biol. 2012 May;61(3):539-42
references.pmid: 22357727
references.citation: Nat Rev Genet. 2009 Sep;10(9):639-50
references.pmid: 19687804
references.citation: Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):15325-9
references.pmid: 24003137
references.citation: Science. 2003 Sep 5;301(5638):1343
references.pmid: 12958352
references.citation: Bioinformatics. 2010 Oct 1;26(19):2455-7
references.pmid: 20671151
references.citation: Immunol Rev. 1998 Dec;166:259-77
references.pmid: 9914918
references.citation: Dis Aquat Organ. 2009 Dec 3;87(3):243-66
references.pmid: 20099417
references.citation: Bioinformatics. 2005 May 15;21(10):2531-3
references.pmid: 15713735
references.citation: Annu Rev Genet. 2007;41:281-304
references.pmid: 18076327
references.citation: Genetics. 2002 Mar;160(3):1231-41
references.pmid: 11901136
references.citation: Dev Comp Immunol. 2011 Sep;35(9):916-23
references.pmid: 21277325
references.citation: Immunogenetics. 2012 Jul;64(7):525-33
references.pmid: 22460528
references.citation: J Evol Biol. 2012 Aug;25(8):1531-42
references.pmid: 22591334
references.citation: Int J Immunogenet. 2014 Oct;41(5):401-12
references.pmid: 25053118
references.citation: Viruses. 2011 Nov;3(11):2065-86
references.pmid: 22163335
references.citation: Mol Ecol. 2006 Aug;15(9):2489-503
references.pmid: 16842422
references.citation: Genetics. 2003 Jul;164(3):1229-36
references.pmid: 12871927
references.citation: Annu Rev Microbiol. 2009;63:291-310
references.pmid: 19575560
references.citation: Eur J Immunol. 1999 Sep;29(9):2897-907
references.pmid: 10508264
references.citation: Mol Ecol. 2009 Mar;18(5):769-81
references.pmid: 19207255
references.citation: Immunogenetics. 2004 Feb;55(11):732-9
references.pmid: 14722687
references.citation: Genetics. 1964 Jan;49(1):49-67
references.pmid: 17248194
references.citation: Evolution. 2002 Oct;56(10):1902-8
references.pmid: 12449477
references.citation: Mol Ecol. 2008 May;17(10):2339-55
references.pmid: 18422929
references.citation: Genomics. 1995 Sep 20;29(2):311-22
references.pmid: 8666377
references.citation: Dev Comp Immunol. 2014 Feb;42(2):311-22
references.pmid: 24135718
references.citation: Annu Rev Genet. 1998;32:415-35
references.pmid: 9928486
references.citation: Immunogenetics. 2005 Nov;57(10):775-81
references.pmid: 16195876
references.citation: Mol Ecol. 2012 Feb;21(4):887-906
references.pmid: 22066802
references.citation: Eur J Immunol. 2001 Feb;31(2):506-15
references.pmid: 11180116
references.citation: Genetics. 2001 Dec;159(4):1833-44
references.pmid: 11779818
references.citation: J Med Chem. 1998 Jul 2;41(14):2481-91
references.pmid: 9651153
references.citation: Bioinformatics. 2005 Mar 1;21(5):676-9
references.pmid: 15509596
references.citation: Proc Biol Sci. 2004 Jan 22;271(1535):197-204
references.pmid: 15058398
references.citation: Mol Biol Evol. 2011 Nov;28(11):3033-43
references.pmid: 21670087
references.citation: Mol Ecol Resour. 2008 Jan;8(1):103-6
references.pmid: 21585727
references.citation: Bioinformatics. 2009 Jun 1;25(11):1451-2
references.pmid: 19346325
references.citation: Int J Immunogenet. 2007 Dec;34(6):475-8
references.pmid: 18001306
references.citation: Theor Appl Genet. 1968 Jun;38(6):226-31
references.pmid: 24442307
references.citation: Cold Spring Harb Protoc. 2009 Aug;2009(8):pdb.emo128
references.pmid: 20147230
references.citation: J Mol Evol. 2008 Jul;67(1):68-75
references.pmid: 18543016
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16221-6
references.pmid: 17911263
references.citation: PLoS One. 2008 Jul 16;3(7):e2692
references.pmid: 18629002
references.citation: PLoS One. 2009;4(2):e4616
references.pmid: 19240796
references.citation: Mol Ecol. 2013 Jan;22(1):111-29
references.pmid: 23062080
references.citation: J Immunol. 2005 Jun 1;174(11):7085-95
references.pmid: 15905552
references.citation: Immunogenetics. 1995;42(5):376-85
references.pmid: 7590971
references.citation: Mol Ecol. 1998 Oct;7(10):1315-22
references.pmid: 9787443
references.citation: Proc Biol Sci. 2012 Dec 22;279(1749):5004-13
references.pmid: 23075838
references.citation: Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16705-10
references.pmid: 21949385
references.citation: Mol Biol Evol. 2006 Feb;23(2):254-67
references.pmid: 16221896
references.citation: Mol Phylogenet Evol. 2013 Dec;69(3):417-29
references.pmid: 23978627
references.citation: Bioinformatics. 2006 Oct 15;22(20):2493-9
references.pmid: 16895925
references.citation: Mol Biol Evol. 2005 May;22(5):1208-22
references.pmid: 15703242
references.citation: PLoS Genet. 2012;8(7):e1002764
references.pmid: 22807683