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BMC evolutionary biology2011; 11; 128; doi: 10.1186/1471-2148-11-128

Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus.

Abstract: Major Histocompatibility Complex (MHC) genes are central to vertebrate immune response and are believed to be under balancing selection by pathogens. This hypothesis has been supported by observations of extremely high polymorphism, elevated nonsynonymous to synonymous base pair substitution rates and trans-species polymorphisms at these loci. In equids, the organization and variability of this gene family has been described, however the full extent of diversity and selection is unknown. As selection is not expected to act uniformly on a functional gene, maximum likelihood codon-based models of selection that allow heterogeneity in selection across codon positions can be valuable for examining MHC gene evolution and the molecular basis for species adaptations. Results: We investigated the evolution of two class II MHC genes of the Equine Lymphocyte Antigen (ELA), DRA and DQA, in the genus Equus with the addition of novel alleles identified in plains zebra (E. quagga, formerly E. burchelli). We found that both genes exhibited a high degree of polymorphism and inter-specific sharing of allele lineages. To our knowledge, DRA allelic diversity was discovered to be higher than has ever been observed in vertebrates. Evidence was also found to support a duplication of the DQA locus. Selection analyses, evaluated in terms of relative rates of nonsynonymous to synonymous mutations (dN/dS) averaged over the gene region, indicated that the majority of codon sites were conserved and under purifying selection (dN <dS). However, the most likely evolutionary codon models allowed for variable rates of selection across codon sites at both loci and, at the DQA, supported the hypothesis of positive selection acting on specific sites. Conclusions: Observations of elevated genetic diversity and trans-species polymorphisms supported the conclusion that balancing selection may be acting on these loci. Furthermore, at the DQA, positive selection was occurring at antigen binding sites, suggesting that a few selected residues may play a significant role in equid immune function. Future studies in natural equid populations will be valuable for understanding the functional significance of the uniquely diverse DRA locus and for elucidating the mechanism maintaining diversity at these MHC loci.
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Publication Date: 2011-05-18 PubMed ID: 21592397PubMed Central: PMC3126738DOI: 10.1186/1471-2148-11-128Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on the investigation of two Major Histocompatibility Complex (MHC) genes evolution in the Equus genus, particularly in equids, and concludes that these genes are under balancing selection, providing invaluable insights into equid immune function.

Understanding Major Histocompatibility Complex (MHC) Genes in Equus Genus

  • This research provides an extensive analysis of the evolution of two MHC genes, DRA and DQA, in the genus Equus. This genus includes horses, zebras, and donkeys.
  • MHC genes play a vital role in the vertebrate immune response. They have notable polymorphism, a high rate of nonsynonymous to synonymous base pair substitution, and trans-species polymorphisms, suggesting the influence of balancing selection by pathogens.
  • The researchers have delved deeper into this area, exploring the full extent of diversity and selection at these loci.

A Focus on DRA and DQA Genes in Equids

  • The focus of the in-depth investigation are two class II MHC genes of the Equine Lymphocyte Antigen (ELA), DRA, and DQA.
  • Significant polymorphism was found in both genes, as well as a substantial amount of inter-specific sharing of allele lineages.
  • DRA exhibited higher allelic diversity than has been previously observed in vertebrates. Additionally, evidence pointed towards a possible duplication of the DQA locus.

Evidence of Balancing Selection

  • With the majority of codon sites being conserved and under purifying selection, an analysis of the relative rates of nonsynonymous to synonymous mutations concluded that balancing selection could be acting on the genes.
  • Furthermore, at the DQA locus, positive selection was occurring at antigen-binding sites. This implies that a few selected residues may be vitally important to equid immune function.
  • The observations of elevated genetic diversity and trans-species polymorphisms further supported the conclusion of the action of balancing selection at these loci.

Implications and Future Directions

  • These findings give insight into a unique aspect of equid immune response, providing a base for future research.
  • Natural equid populations’ study holds the potential to better understand the functional significance of the DRA locus’ unique diversity and shed light on the mechanism maintaining diversity at these MHC loci.

Cite This Article

APA
Kamath PL, Getz WM. (2011). Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus. BMC Evol Biol, 11, 128. https://doi.org/10.1186/1471-2148-11-128

Publication

BMC evolutionary biology
ISSN: 1471-2148
NlmUniqueID: 100966975
Country: England
Language: English
Volume: 11
Pages: 128

Researcher Affiliations

Kamath, Pauline L
  • Department of Environmental Science, Policy and Management, University of California Berkeley, USA. pkamath@berkeley.edu
Getz, Wayne M

    MeSH Terms

    • Alleles
    • Amino Acid Sequence
    • Animals
    • Equidae / genetics
    • Evolution, Molecular
    • Genes, MHC Class II
    • Genetic Variation
    • Molecular Sequence Data
    • Phylogeny
    • Sequence Alignment

    Grant Funding

    • GM083863 / NIGMS NIH HHS

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