Hey, J. | bioRxiv Science

bioRxiv2018

Age distributions of rare lineages reveal recent demographic history and selection

The age of an allele of a given frequency offers insight into both its function and origin, and the distribution of ages of alleles in a population conveys significant information about its history. The rarer the allele the more likely it is to reveal functional biological insight and the more recent the historical revelation. By measuring the length of the haplotype shared between an individual carrying a rare variant and its closest relative not carrying the variant we are able to approximate the age of the variant and can apply this method even when only a single copy of a variant has been sampled in a population. Applying this technique to rare variants in a large population sample from the United Kingdom, we identify historical migration from West Africa approximately 400 years ago, evidence of direct selection against novel protein-altering rare variants in individual biological pathways, continued negative frequency dependent selection on protein-altering variants in olfactory transducers and the innate immune system, and map the impact of background selection on the most recent portions of the sample genealogy.

genomics↗

bioRxiv2017

Recent African gene flow responsible for excess of old rare genetic variation in Great Britain

Population genomic studies can reveal the allele frequencies at millions of SNPs, with the numbers of observed low frequency SNPs increasing as more genomes are sequenced. Rare alleles tend to be younger than common alleles and are especially useful for studying demographic history, selection and heritability1,2. However, allele frequency can be a poor proxy for allele age, as genetic drift and natural selection can lead to alleles that are both rare and old. In order to allow joint assessments of allele frequency and allele age, a new estimator of allele age was developed that can be applied to variants of the lowest observed frequencies (singletons). By examining the geographic and age distribution of very rare variants in a large genomic sample from the UK3, we identify new evidence of gene flow from Africa into the ancestors of the modern UK population. A substantial proportion of variants with observed frequencies as low as 1.4 x 10-4 are orders of magnitude older than can be explained without African gene flow and are found at much higher frequencies within modern African populations. We estimate that African populations contributed approximately 1.2% of the UK gene pool and did so approximately 400 years ago. These findings are relevant both to our understanding of human history and to the nature of rare variation segregating within populations: a variant that is rare because it is a recent mutation in the direct ancestor of the population will have had a very different evolutionary history than an ancient one that has persisted at high frequencies in a diverged population and only recently arrived through migration.

genomics↗