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.

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Acknowledgments

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.

Ethical approval

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.

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Correspondence to Karen E. Tracy.

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Tracy, K.E., Kiemnec-Tyburczy, K.M., DeWoody, J.A. et al. Positive selection drives the evolution of a major histocompatibility complex gene in an endangered Mexican salamander species complex. Immunogenetics 67, 323–335 (2015). https://doi.org/10.1007/s00251-015-0835-4

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Keywords

  • Ambystoma
  • Balancing selection
  • Disease
  • Immunogenetics
  • MHC