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Elucidating the origin of HLA-B*73 allelic lineage: Did modern humans benefit by archaic introgression?

ABSTRACT: A previous study reported that some of the human leukocyte antigen (HLA) alleles and haplotypes in present-day humans were acquired by admixture with archaic humans; specifically, an exceptionally diverged HLA-B*73 allele was proposed to be transmitted from Denisovans, although the DNA sequence of HLA-B*73 has not been detected in the Denisovan genome. Here, we argue against the hypothesis that HLA-B*73 introgressed from Denisovans into early modern humans. A phylogenetic analysis revealed that HLA-B*73:01 formed a monophyletic group with a chimpanzee MHC-B allele, strongly suggesting that the HLA-B*73 allelic lineage has been maintained in humans as well as in chimpanzees since the divergence of humans and chimpanzees. The global distribution of HLA-B*73 allele showed that the population frequency of HLA-B*73 in west Asia (0.24 %)-a possible site of admixture with Denisovans-is lower than that in Europe (0.72 %) and in south Asia (0.69 %). Furthermore, HLA-B*73 is not observed in Melanesia even though the Melanesian genome contains the highest proportion of Denisovan ancestry in present-day human populations. Single nucleotide polymorphisms in HLA-A*11-HLA-C*12:02 or HLA-A*11-C*15 haplotypes, one of which was assumed to be transmitted together with HLA-B*73 from Denisovans by the study of Abi-Rached and colleagues, were not differentiated from those in other HLA-A-C haplotypes in modern humans. These results do not support the introgression hypothesis. Thus, we conclude that it is highly likely that HLA-B*73 allelic lineage has been maintained in the direct ancestors of modern humans.

SUBMITTER: Yasukochi Y

PROVIDER: S-EPMC5203853 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Elucidating the origin of HLA-B*73 allelic lineage: Did modern humans benefit by archaic introgression?

Yasukochi Yoshiki Y Ohashi Jun J

Immunogenetics 20160930 1

A previous study reported that some of the human leukocyte antigen (HLA) alleles and haplotypes in present-day humans were acquired by admixture with archaic humans; specifically, an exceptionally diverged HLA-B*73 allele was proposed to be transmitted from Denisovans, although the DNA sequence of HLA-B*73 has not been detected in the Denisovan genome. Here, we argue against the hypothesis that HLA-B*73 introgressed from Denisovans into early modern humans. A phylogenetic analysis revealed that ...[more]

PMID: 27695917

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Project description:BackgroundIntrogression from extinct Neanderthal and Denisovan human species has been shown to contribute to the genetic pool of modern human populations and their phenotypic spectrum. Evidence of how Neanderthal introgression shaped the genetics of human traits and diseases has been extensively studied in populations of European descent, with signatures of admixture reported for instance in genes associated with pigmentation, immunity, and metabolic traits. However, limited information is currently available about the impact of archaic introgression on other ancestry groups. Additionally, to date, no study has been conducted with respect to the impact of Denisovan introgression on the health and disease of modern populations. Here, we compare the way evolutionary pressures shaped the genetics of complex traits in East Asian and European populations, and provide evidence of the impact of Denisovan introgression on the health of East Asian and Central/South Asian populations.ResultsLeveraging genome-wide association statistics from the Biobank Japan and UK Biobank, we assessed whether Denisovan and Neanderthal introgression together with other evolutionary genomic signatures were enriched for the heritability of physiological and pathological conditions in populations of East Asian and European descent. In EAS, Denisovan-introgressed loci were enriched for coronary artery disease heritability (1.69-fold enrichment, p=0.003). No enrichment for archaic introgression was observed in EUR. We also performed a phenome-wide association study of Denisovan and Neanderthal alleles in six ancestry groups available in the UK Biobank. In EAS, the Denisovan-introgressed SNP rs62391664 in the major histocompatibility complex region was associated with albumin/globulin ratio (beta=-0.17, p=3.57×10-7). Neanderthal-introgressed alleles were associated with psychiatric and cognitive traits in EAS (e.g., "No Bipolar or Depression"-rs79043717 beta=-1.5, p=1.1×10-7), and with blood biomarkers (e.g., alkaline phosphatase-rs11244089 beta=0.1, p=3.69×10-116) and red hair color (rs60733936 beta=-0.86, p=4.49×10-165) in EUR. In the other ancestry groups, Neanderthal alleles were associated with several traits, also including the use of certain medications (e.g., Central/South East Asia: indapamide - rs732632 beta=-2.38, p=5.22×10-7).ConclusionsOur study provides novel evidence regarding the impact of archaic introgression on the genetics of complex traits in worldwide populations, highlighting the specific contribution of Denisovan introgression in EAS populations.

Dataset Information

Elucidating the origin of HLA-B*73 allelic lineage: Did modern humans benefit by archaic introgression?

Publications

Elucidating the origin of HLA-B*73 allelic lineage: Did modern humans benefit by archaic introgression?

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