Molecular evolution of genes encoding allergen proteins in the peanuts genus Arachis: Structural and functional implications

dc.contributor.authorHilu, Khidir W.en
dc.contributor.authorFriend, Sheena A.en
dc.contributor.authorVallanadu, Viruthikaen
dc.contributor.authorBrown, Anne M.en
dc.contributor.authorHollingsworth, Louis R. IVen
dc.contributor.departmentUniversity Librariesen
dc.contributor.departmentBiological Sciencesen
dc.description.abstractFood allergies are severe immune responses to plant and animal products mediated by immunoglobulin E (IgE). Peanuts (Arachis hypogaea L.) are among the top 15 crops that feed the world. However, peanuts is among the “big eight food allergens”, and allergies induced by peanuts are a significant public health problem and a life-threatening concern. Targeted mutation studies in peanuts demonstrate that single residue alterations in these allergen proteins could result in substantial reduction in allergenicity. Knowledge of peanut allergen proteins is confined to the allotetraploid crop and its two progenitors. We explored frequencies and positions of natural mutations in the hyperallergenic homologues Ara h 2 and Ara h 6 in newly generated sequences for 24 Arachis wild species and the crop species, assessed potential mutational impact on allergenicity using immunoblots and structural modeling, and evaluated whether these mutations follow evolutionary trends. We uncovered a wealth of natural mutations, both substitutions and gaps, including the elimination of immunodominant epitopes in some species. These molecular alterations appear to be associated with substantial reductions in allergenicity. The study demonstrated that Ara h 2 and Ara h 6 follow contrasting modes of natural selection and opposing mutational patterns, particularly in epitope regions. Phylogenetic analysis revealed a progressive trend towards immunodominant epitope evolution in Ara h 2. The findings provide valuable insight into the interactions among mutations, protein structure and immune system response, thus presenting a valuable platform for future manipulation of allergens to minimize, treat or eliminate allergenicity. The study strongly encourages exploration of genepools of economically important plants in allergenicity research.en
dc.description.sponsorshipThe Virginia Tech University Libraries Open Access Subvention Fund supported the open access publication of this paper (the funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript).en
dc.format.extent22 pagesen
dc.identifier.citationHilu KW, Friend SA, Vallanadu V, Brown AM, Hollingsworth LR, IV, Bevan DR (2019) Molecular evolution of genes encoding allergen proteins in the peanuts genus Arachis: Structural and functional implications. PLoS ONE 14(11): e0222440.
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.titleMolecular evolution of genes encoding allergen proteins in the peanuts genus Arachis: Structural and functional implicationsen
dc.title.serialPLOS Oneen
dc.typeArticle - Refereeden


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