English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Genetic diversity in human leukocyte antigen ( HLA ) molecules is thought to have arisen from the co‐evolution between host and pathogen and maintained by balancing selection. Heterozygote advantage is a common proposed scenario for maintaining high levels of diversity in  HLA  genes, and extending from this, the divergent allele advantage ( DAA ) model suggests that individuals with more divergent  HLA  alleles bind and recognize a wider array of antigens. While the  DAA  model seems biologically suitable for driving  HLA  diversity, there is likely an upper threshold to the amount of sequence divergence. We used peptide‐binding and pathogen‐recognition capacity of   DRB1   alleles as a model to further explore the  DAA  model; within the   DRB1   locus, we examined binding predictions based on two distinct phylogenetic groups (denoted group A and B) previously identified based on non‐peptide‐binding region ( PBR ) nucleotide sequences. Predictions in this study support that group A allele and group B allele lineages have contrasting binding/recognition capacity, with only the latter supporting the  DAA  model. Furthermore, computer simulations revealed an inconsistency in the  DAA  model alone with observed extent of polymorphisms, supporting that the  DAA  model could only work effectively in combination with other mechanisms. Overall, we support that the mechanisms driving  HLA  diversity are non‐exclusive. By investigating the relationships among  HLA  alleles, and pathogens recognized, we can provide further insights into the mechanisms on how humans have adapted to infectious diseases over time.

A limit to the divergent allele advantage model supported by variable pathogen recognition across HLA‐DRB1 allele lineages