Figure 4. Selection scenarios before and after European Contact.

(a) Distribution of PBS scores for long-term balancing selection (heterozygote advantage) simulations involving a genomic region of the same length as the HLA-DQA1 transcript. Given the observed PBS score in the ancient population, this form of balancing selection is inconsistent with our data. (b) Empirical distribution of frequency changes for all derived alleles in the exome between the ancient and modern populations, showing the HLA-DQA1 UTR5 SNPs as outliers. (c) Simulations of different selection schemes and the allele frequency of the HLA-DQA1 SNPs observed in the modern Tsimshian. The allele frequency changes between the ancient and modern populations could not be explained by our demographic model (shift due to neutrality after European contact) or one that included only positive selection (no shift from positive selection after European contact). None of the simulations in which the originally positively-selected allele is neutral or still under positive selection after the time of European contact reached the observed allele frequency in the modern population. A model that incorporated negative selection after European contact was a better fit to our data, where ∼26% of the simulations reached the observed frequency.