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Admixture-enabled Selection for Rapid Adaptive Evolution in the Americas

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Admixture-enabled Selection for Rapid Adaptive Evolution in the Americas

Emily T Norris et al. Genome Biol.

Abstract

Background: Admixture occurs when previously isolated populations come together and exchange genetic material. We hypothesize that admixture can enable rapid adaptive evolution in human populations by introducing novel genetic variants (haplotypes) at intermediate frequencies, and we test this hypothesis through the analysis of whole genome sequences sampled from admixed Latin American populations in Colombia, Mexico, Peru, and Puerto Rico.

Results: Our screen for admixture-enabled selection relies on the identification of loci that contain more or less ancestry from a given source population than would be expected given the genome-wide ancestry frequencies. We employ a combined evidence approach to evaluate levels of ancestry enrichment at single loci across multiple populations and multiple loci that function together to encode polygenic traits. We find cross-population signals of African ancestry enrichment at the major histocompatibility locus on chromosome 6, consistent with admixture-enabled selection for enhanced adaptive immune response. Several of the human leukocyte antigen genes at this locus, such as HLA-A, HLA-DRB51, and HLA-DRB5, show independent evidence of positive selection prior to admixture, based on extended haplotype homozygosity in African populations. A number of traits related to inflammation, blood metabolites, and both the innate and adaptive immune system show evidence of admixture-enabled polygenic selection in Latin American populations.

Conclusions: The results reported here, considered together with the ubiquity of admixture in human evolution, suggest that admixture serves as a fundamental mechanism that drives rapid adaptive evolution in human populations.

Keywords: Admixture; Genetic ancestry; Polygenic traits; Population genomics; Positive selection; Rapid adaptive evolution.

Conflict of interest statement

The authors declare that they have no competing interests

Figures

Fig. 1
Fig. 1
Genetic ancestry and admixture in Latin America. a The global locations of the four LA populations analyzed here (green) are shown along with the locations of the African (blue), European (orange), and Native American (red) reference populations. The sources of the genomic data are indicated in the key. b ADMIXTURE plot showing the three-way continental ancestry components for individuals from the four LA populations—Colombia, Mexico, Peru, and Puerto Rico—compared to global reference populations. c The mean (±se) continental ancestry fractions for the four LA populations. d Chromosome painting showing the genomic locations of ancestry-specific haplotypes for an admixed LA genome.
Fig. 2
Fig. 2
African ancestry enrichment at the major histocompatibility complex (MHC) locus. a Manhattan plot showing the statistical significance of African ancestry enrichment across the genome. b Haplotype on chromosome 6 with significant African ancestry enrichment for three of the four LA populations: Colombia, Mexico, and Puerto Rico. This region corresponds to the largest peak of African ancestry enrichment on chromosome 6 seen in a. Population-specific African (blue), European (orange), and Native American (red) ancestry enrichment values (zanc) are shown for chromosome 6 and the MHC locus. c Integrated haplotype score (iHS) values for African continental population from the 1KGP are shown for the MHC locus; peaks correspond to putative positively selected human leukocyte antigen (HLA) genes.
Fig. 3
Fig. 3
Admixture-enabled selection at human leukocyte antigen (HLA) genes. Integrated haplotype score (iHS) peaks for the African continental population from the 1KGP are shown for a the MHC Class I gene HLA-A and b the MHC Class II genes HLA-DRB5 and HLA-DRB1. c Illustration of the MHC Class I and MHC Class II antigen presenting pathways, with African enriched genes shown in blue.
Fig. 4
Fig. 4
Model of ancestry-enabled selection at the MHC locus in the Colombia population. a Modeled levels of ancestry enrichment and depletion (zanc, y-axis) corresponding to a range of different selection coefficients (s, x-axis): African (blue), European (orange), and Native American (red). The intersection of the observed level of African ancestry enrichment at the MHC locus and the corresponding s value is indicated with dashed lines. b The trajectory of predicted ancestry enrichment and depletion (zanc,y-axis) over time (t generations, x-axis) is shown for the inferred selection coefficient of s = 0.05.
Fig. 5
Fig. 5
Polygenic ancestry enrichment (PAE) and admixture-enabled selection. a Distributions of the PAE test statistic are shown for each of the three ancestry components—African (blue), European (orange), and Native American (red)—across the four LA populations. Points beyond the dashed lines correspond to polygenic traits with statistically significant PAE values, after correction for multiple tests. b Polygenic traits that show evidence of PAE in multiple LA populations. PAE values are color coded as shown in the key, and the ancestry components are indicated for each trait. Immune system traits are divided into adaptive (purple), innate (green), or both (blue).
Fig. 6.
Fig. 6.
Innate immune system pathways showing Native American ancestry enrichment. Illustration of three interconnected pathways from the innate immune system—the RIG-I-like receptor signaling pathway, the Toll-like receptor signaling pathway, and the cytosolic DNA-sensing pathway—highlighting genes (proteins) that show Native American ancestry enrichment

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