Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency Data

TLDR

Genetic data–derived demographic models illuminate prehistorical events and serve as null models for selection scans. The study introduces a method to infer demographic history using the joint allele‑frequency spectrum across populations. The method numerically computes the expected joint spectrum via a diffusion approximation of the Wright–Fisher process for up to three populations, applies a composite likelihood framework with linkage‑aware bootstrapping to estimate uncertainties, and can incorporate selection to predict allele distributions under expansions, contractions, migrations, and admixture. Applied to 5 Mb of noncoding DNA from 68 individuals in four populations, the method reconstructs human out‑of‑Africa expansion and New World settlement, and accurately predicts nonsynonymous variant frequencies when combined with a distribution of selective effects across YRI, CHB, and CEU.

Abstract

Demographic models built from genetic data play important roles in illuminating prehistorical events and serving as null models in genome scans for selection. We introduce an inference method based on the joint frequency spectrum of genetic variants within and between populations. For candidate models we numerically compute the expected spectrum using a diffusion approximation to the one-locus two-allele Wright-Fisher process, involving up to three simultaneous populations. Our approach is a composite likelihood scheme, since linkage between neutral loci alters the variance but not the expectation of the frequency spectrum. We thus use bootstraps incorporating linkage to estimate uncertainties for parameters and significance values for hypothesis tests. Our method can also incorporate selection on single sites, predicting the joint distribution of selected alleles among populations experiencing a bevy of evolutionary forces, including expansions, contractions, migrations, and admixture. As applications, we model human expansion out of Africa and the settlement of the New World, using 5 Mb of noncoding DNA resequenced in 68 individuals from 4 populations (YRI, CHB, CEU, and MXL) by the Environmental Genome Project. We also combine our demographic model with a previously estimated distribution of selective effects among newly arising amino acid mutations to accurately predict the frequency spectrum of nonsynonymous variants across three continental populations (YRI, CHB, CEU).