Positive selection drives the evolution of a major histocompatibility complex gene in an endangered Mexican salamander species complex
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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.
KeywordsAmbystoma Balancing selection Disease Immunogenetics MHC
We thank D. Weisrock for providing A. dumerilii tissue samples for this study, A. E. Savage and D. Rodriguez for the assistance with molecular protocols, R. C. Bell for the assistance with phylogenetic analyses, A. Ellison for supertyping of MHC, and M. Yuan for the assistance with figures. Members of the Zamudio lab group provided invaluable advice and feedback throughout this study. We also thank our two anonymous reviewers for their feedback, which greatly improved the final version of the manuscript. Funding for this study was provided by National Science Foundation Grants (DEB-0815315 and DEB-1120249 to K. R. Zamudio) and an award from the Dextra Undergraduate Research Endowment Fund (to K. E. Tracy).
Conflict of interest
The authors declare that they have no conflict of interest.
The tissues used for this study were collected by Gabriela Parra-Olea (Parra-Olea et al. 2012). Tissues were collected under the permit FAUT-0106, issued by Secretaria del Medio Ambiente y Recursos Naturales and protocol #1999-0010 issued by the Cornell University Institutional Animal Care and Use Committee.
- Frank SA (2002) Genetic variability of hosts. http://www.ncbi.nlm.nih.gov/books/NBK2401/. Accessed 3 May 2014
- Frost, DR (2014) Amphibian species of the world: an online reference. Version 6.0. AmericanGoogle Scholar
- Goudet J (1995) FSTAT (Version 1.2): a computer program to calculate F-statistics. J Hered 86:485–486Google Scholar
- Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98Google Scholar
- Hammer O, Harper DAT, Ryan PD (2001) PAST: paleontological statistics software package for education and data analysis. Palaeontol Electron 4:UnpaginatedGoogle Scholar
- Irschick DJ, Shaffer HB (1997) The polytypic species revisited: morphological differentiation among tiger salamanders (Ambystoma tigrinum) (Amphibia: Caudata). Herpetologica 53:30–49Google Scholar
- IUCN (2014) The IUCN red list of threatened species. Version 2014.2. http://www.iucnredlist.org. Accessed 21 Oct 2014
- Klein J (1986) Natural history of the major histocompatibility complex. New YorkGoogle Scholar
- Klein J, Sato A, Nikolaidis N (2007) MHC, TSP, and the origin of species: from immunogenetics to evolutionary genetics. In: Campbell A (ed) Annual review of genetics book series. California Annual Reviews, Palo Alto, pp 281–304Google Scholar
- Laurens V, Chapusot C, del Rosario OM et al (2001) Axolotl MHC class II β chain: predominance of one allele and alternative splicing of the β1 domain. Eur J Immunol 31:506–515. doi: 10.1002/1521-4141(200102)31:2<506::AID-IMMU506>3.0.CO;2-P CrossRefPubMedGoogle Scholar
- Parham P, Janeway CA (2005) The immune system. Garland Science, New YorkGoogle Scholar
- Raymond M, Rousset F (1995) GENEPOP (Version 1.2): population genetics software for exact tests and ecumenicism. J Hered 86:248–249Google Scholar
- Sammut B, Du Pasquier L, Ducoroy P et al (1999) Axolotl MHC architecture and polymorphism. Eur J Immunol 29:2897–2907. doi: 10.1002/(SICI)1521-4141(199909)29:09<2897::AID-IMMU2897>3.0.CO;2-2 CrossRefPubMedGoogle Scholar
- Swofford D (2003) PAUP*. Phylogenetic analysis using parsimony (*and other methods). Version 4. Sinauer, Sunderland, MassachusettsGoogle Scholar
- Teacher AGF, Garner TWJ, Nichols RA (2009) Evidence for directional selection at a novel major histocompatibility class I marker in wild common frogs (Rana temporaria) exposed to a viral pathogen (Ranavirus). PLoS One 4:e4616. doi: 10.1371/journal.pone.0004616 CrossRefPubMedCentralPubMedGoogle Scholar
- Voss SR, Epperlein HH, Tanaka EM (2009) Ambystoma mexicanum, the axolotl: a versatile amphibian model for regeneration, development, and evolution studies. Cold Spring Harb Protoc 2009:pdb.emo128. doi: 10.1101/pdb.emo128