Estimates of continental ancestry vary widely among individuals with the same mtDNA haplogroup

Abstract

The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual's place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual's mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin.

Figure 1

Geographic Location, mtDNA-Haplogroup Frequencies, and Average Ancestry Proportions in the HGDP Populations (A) World map showing sample locations (points) for each of the populations included in the HGDP (labels). (B) Left column: barplots of continental-ancestry proportions averaged within each HGDP population. Barplots are colored by continental region (labeled by colored bars on the left) and sorted by continental ancestry. Right column: barplots of haplogroup frequencies within each population. Barplots are colored by mtDNA haplogroup (labeled by the haplogroup tree in C). (C) Barplots of continental-ancestry proportions averaged within each mtDNA haplogroup within the HGDP dataset. Barplots are colored by continental region (labeled by colored bars on the left of A). The unscaled phylogeny on the left shows the relationships between the mtDNA haplogroups.

Figure 2

Individual Continental-Ancestry Proportions within Each Haplogroup in the HGDP Each horizontal line is a barplot for a single HGDP sample and indicates individual continental-ancestry proportions. Continental regions are colored according to the key at the top. Individual barplots are grouped into the 23 mtDNA haplogroups as indicated on the top left. Each haplogroup is labeled with the mean pairwise Euclidean distance (see Material and Methods), and haplogroups are sorted by increasing mean pairwise Euclidean distance from top to bottom and left to right.

Figure 3

mtDNA-Haplogroup Frequencies, Population-Averaged and Haplogroup-Averaged Continental-Ancestry Proportions, and Individual Continental-Ancestry Proportions in the 1KGP Samples (A) Left column: barplots of continental-ancestry proportions averaged within each 1KGP population. Barplots are colored by continental region (labeled by colored bars in Figure 1A) and sorted by continental ancestry. Right column: barplots of mtDNA-haplogroup frequencies within each population. Barplots are colored by haplogroup (labeled by the haplogroup boxes in B). (B) Barplots of continental-ancestry proportions averaged within each mtDNA haplogroup within the 1KGP. Barplots are colored by continental region (see key at bottom). The unscaled phylogeny on the left is the same as in Figure 1C. Numbers to the right of haplogroup labels are the sample size for each haplogroup. Some haplogroups were not observed in the 1KGP samples. (C) Individual continental-ancestry proportions within each haplogroup. Each horizontal line is a barplot for a single 1KGP sample and indicates individual continental-ancestry proportions. Continental regions are colored according to the key at bottom. Individual barplots are grouped into mtDNA haplogroups as indicated on the top left. Each haplogroup is labeled with the mean pairwise Euclidean distance (see Material and Methods), and haplogroups are sorted by increasing mean pairwise Euclidean distance from top to bottom and left to right. NA indicates not available.

Figure 4

Misclassification Probabilities in the HGDP and 1KGP Each cell (row i, column j) denotes the probability that a sample experimentally determined as haplogroup i is classified as haplogroup j on the basis of a fitted logit model. Cells are colored by increasing classification probabilities from white to blue (see key at bottom). Diagonal entries (gray outlines) are the probability of being classified correctly. Barplots on the right show the average probability of misclassification for each haplogroup, which is the total of all non-diagonal values in each row. The top 10% of non-zero classification probabilities are labeled (white text). (A) Misclassification in the HGDP. (B) Misclassification in the 1KGP.

Figure 5

mtDNA-Haplogroup Membership Might Not Be Associated with Autosomal Ancestry Proportions Each point on the map marks a sampled population, and the population’s mtDNA-haplogroup frequencies are shown in the horizontal barplots below (color key corresponds to haplogroups in Figures 1C and 3B). One individual from each population, along with a vertical barplot of the individual’s autosomal-ancestry proportions, is shown below the map. The two individuals from haplogroup R9 have highly similar autosomal-ancestry proportions, whereas those from haplogroup J are very different.