Demographic history and selection at HLA loci in Native Americans

Abstract

The American continent was the last to be occupied by modern humans, and native populations bear the marks of recent expansions, bottlenecks, natural selection, and population substructure. Here we investigate how this demographic history has shaped genetic variation at the strongly selected HLA loci. In order to disentangle the relative contributions of selection and demography process, we assembled a dataset with genome-wide microsatellites and HLA-A , -B , -C , and - DRB1 typing data for a set of 424 Native American individuals. We find that demographic history explains a sizeable fraction of HLA variation, both within and among populations. A striking feature of HLA variation in the Americas is the existence of alleles which are present in the continent but either absent or very rare elsewhere in the world. We show that this feature is consistent with demographic history (i.e., the combination of changes in population size associated with bottlenecks and subsequent population expansions). However, signatures of selection at HLA loci are still visible, with significant evidence selection at deeper timescales for most loci and populations, as well as population differentiation at HLA loci exceeding that seen at neutral markers.

HLA allele-calling using whole-exome sequencing identifies 129 novel associations in 11 autoimmune diseases: a multi-ancestry analysis in the UK Biobank

“…1B ). The finding that the AMR participants have a larger number of HLA alleles is consistent with other studies and reference panels which showed that native American populations have a high number of HLA alleles absent in other populations 20–22 . As expected, most of the HLA alleles were rare (minor allele frequency [MAF] < 1%) in all ancestries, with 166 out of 5,295 alleles with MAF > 1% in the EUR cohort and 209 out of 1,304 alleles with MAF > 1% in the AMR cohort (supplementary figure SF2 ).…”

Bioinformatics Prediction of SARS-CoV-2 Epitopes as Vaccine Candidates for the Colombian Population

“…The dataset of HLA I alleles used for epitope prediction included: (1) HLA-A, HLA-B and HLA-C alleles that presented the top ten highest frequencies in the Colombian general population (Dataset: Colombia-Bogotá). As well as, (2) the HLA-A, HLA-B and HLA-C alleles that exhibited the highest frequency for each of the eleven Colombian Amerindian groups with HLA I frequencies reported in the AFND [28], which coincided with the results of the literature search [29][30][31]. These Amerindian groups were: Arhuaco, Embera, Inga, Kogi, Chimila Norte, Wiwa Norte, Waunana, Wayyu, Zenú, Ticuna Arara, and Ticuna Tarapaca.…”

An HLA map of the world: A comparison of HLA frequencies in 200 worldwide populations reveals diverse patterns for class I and class II

“…Of note, these populations also show the highest number of private HLA-DRB1 alleles ( Gonzalez-Galarza et al, 2021 ), which account for a high proportion of their allele pools ( Meyer et al, 2006 ) and are thought to be the result of selective forces acting in a context of severely reduced HLA diversity ( Titus-Trachtenberg et al, 1994 ; Erlich et al, 1997 ; Hollenbach et al, 2001 ). In fact, a mixture of long-term balancing selection and a combination of episodes of more recent positive and balancing selection has been associated with simultaneously increasing intra-population diversity and inter-population differentiation in Native Americans ( Single et al, 2020 ; Nunes et al, 2021 ).…”