PMID- 31675366
OWN - NLM
STAT- MEDLINE
DCOM- 20200319
LR  - 20200319
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 14
IP  - 11
DP  - 2019
TI  - Molecular evolution of genes encoding allergen proteins in the peanuts genus 
      Arachis: Structural and functional implications.
PG  - e0222440
LID - 10.1371/journal.pone.0222440 [doi]
LID - e0222440
AB  - Food 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.
FAU - Hilu, Khidir W
AU  - Hilu KW
AUID- ORCID: 0000-0001-5881-6094
AD  - Department of Biological Sciences, Virginia Tech, Blacksburg, VA, United States 
      of America.
FAU - Friend, Sheena A
AU  - Friend SA
AD  - Department of Biological Sciences, Virginia Tech, Blacksburg, VA, United States 
      of America.
FAU - Vallanadu, Viruthika
AU  - Vallanadu V
AD  - Department of Biological Sciences, Virginia Tech, Blacksburg, VA, United States 
      of America.
FAU - Brown, Anne M
AU  - Brown AM
AUID- ORCID: 0000-0001-6951-8228
AD  - Research and Informatics, Virginia Tech, Blacksburg, VA, United States of 
      America.
AD  - Department of Biochemistry, Virginia Tech, Blacksburg, VA, United States of 
      America.
FAU - Hollingsworth, Louis R 4th
AU  - Hollingsworth LR 4th
AUID- ORCID: 0000-0002-4130-3580
AD  - Department of Biochemistry, Virginia Tech, Blacksburg, VA, United States of 
      America.
FAU - Bevan, David R
AU  - Bevan DR
AD  - Department of Biochemistry, Virginia Tech, Blacksburg, VA, United States of 
      America.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191101
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Allergens)
RN  - 0 (Epitopes)
RN  - 0 (Plant Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Allergens/*genetics/metabolism
MH  - Arachis/*genetics/metabolism
MH  - Crops, Agricultural/genetics/metabolism
MH  - Epitopes
MH  - *Evolution, Molecular
MH  - Humans
MH  - Models, Molecular
MH  - Mutation
MH  - Peanut Hypersensitivity/*immunology
MH  - Phylogeny
MH  - Plant Proteins/*genetics/metabolism
MH  - Sequence Homology
MH  - Young Adult
PMC - PMC6824556
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/11/02 06:00
MHDA- 2020/03/20 06:00
PMCR- 2019/11/01
CRDT- 2019/11/02 06:00
PHST- 2019/06/07 00:00 [received]
PHST- 2019/08/29 00:00 [accepted]
PHST- 2019/11/02 06:00 [entrez]
PHST- 2019/11/02 06:00 [pubmed]
PHST- 2020/03/20 06:00 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
AID - PONE-D-19-16216 [pii]
AID - 10.1371/journal.pone.0222440 [doi]
PST - epublish
SO  - PLoS One. 2019 Nov 1;14(11):e0222440. doi: 10.1371/journal.pone.0222440. 
      eCollection 2019.