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/

Global: Zendy Plus annual

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

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background  Diversity among human leukocyte antigen (HLA) molecules has been maintained by host-pathogen coevolution over a long period of time. Reflecting this diversity, the  HLA  loci are the most polymorphic in the human genome. One characteristic of  HLA  diversity is long-term persistence of allelic lineages, which causes trans-species polymorphisms to be shared among closely related species. Modern humans have disseminated across the world after their exodus from Africa, while chimpanzees have remained in Africa since the speciation event between humans and chimpanzees. It is thought that modern humans have recently acquired resistance to novel pathogens outside Africa. In the present study, we investigated  HLA  alleles that could contribute to this local adaptation in humans and also studied the contribution of natural selection to human evolution by using molecular data.    Results  Phylogenetic analysis of  HLA-DRB1  genes identified two major groups,  HLA  Groups A and B. Group A formed a monophyletic clade distinct from  DRB1  alleles in other Catarrhini, suggesting that Group A is a human-specific allelic group. Our estimates of divergence time suggested that seven  HLA-DRB1  Group A allelic lineages in humans have been maintained since before the speciation event between humans and chimpanzees, while chimpanzees possess only one  DRB1  allelic lineage ( Patr-DRB1*03 ), which is a sister group to Group A. Experimental data showed that some Group A alleles bound to peptides derived from human-specific pathogens. Of the Group A alleles, three exist at high frequencies in several local populations outside Africa.    Conclusions   HLA  Group A alleles are likely to have been retained in human lineages for a long period of time and have not expanded since the divergence of humans and chimpanzees. On the other hand, most orthologs of  HLA  Group A alleles may have been lost in the chimpanzee due to differences in selective pressures. The presence of alleles with high frequency outside of Africa suggests these HLA molecules result from the local adaptations of humans. Our study helps elucidate the mechanism by which the human adaptive immune system has coevolved with pathogens over a long period of time.

A human-specific allelic group of the MHC DRB1 gene in primates