Ancestral components of admixed genomes in a Mexican cohort

Abstract

For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study "virtual genomes" of admixed individuals. We apply this approach to a cohort of 492 parent-offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations-Africa, Europe, and America-vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10-15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people.

Figure 1. Schematic describing the analytic framework for characterizing continental-level and within-continent populations structure in an admixed population.

For virtual genomes, haplotypes from all but one ancestral population are “masked” as missing data.

Figure 2. Continental-level ancestry proportions and admixing time.

(A) Individual ancestry proportions (red = European; yellow = Indigenous American, blue = African). (B) Histogram comparing the Indigenous American ancestry in the Mexico City cohort (Mex1) and Los Angeles cohort (Mex2). (C) Principal component analysis of the Mexican individuals from Mexico City and Los Angeles, CA. Red and blue circles indicate the location of the HapMap CEU and YRI individuals, respectively. Gray points represent admixed individuals; virtual genomes, Mex^AMR (yellow), Mex^EUR (blue) and Mex^EUR (red) are projected to the PC plot. (D) Admixing times estimated by the number of ancestry blocks. The number of European (vs non-European) ancestry blocks is plotted against European ancestry (red); analogously, the numbers of Indigenous American (vs non-Indigenous American) blocks are plotted against the Indigenous American ancestry (yellow). Each curve represents the expected number of such blocks for a specific admixing time (in generations).

Figure 3. Population structure within the European and Indigenous American components of Mexican genomes.

(A) Principal component analysis of the European chromosomal segments traces the ancestry origin closest to Portuguese. (B) Principal component analysis of Indigenous American segments, HapMap CEU and various Indigenous American populations. (C) Same as (B), with CEU individuals removed. (D) Same as (B), with CEU, Surui, Karitiana and Pima removed. The arrow highlights a Mexican individual whose ancestry is traced to the South American group of Aymara.

Figure 4. Signatures of recent positive selection.

(A) Overlap of top 1% SNPs (with |iHS|>2.5) in Mex^EUR and Mex^AMR. (B) Overlap of SNPs with |iHS|>2.5 in Mex^AMR, HapMap CEU and YRI . (C) Overlap of SNPs with |iHS|>2.5 in Mex^EUR, HapMap CEU and YRI. Numbers in red denotes significant enrichment in overlap.