Neutral genomic regions refine models of recent rapid human population growth
Elodie Gazave, Li Ma, Diana Chang, Alex Coventry, Feng Gao, Donna Muzny, Eric Boerwinkle, Richard Gibbs, Charles F. Sing, Andrew G. Clark, Alon Keinan
(Submitted on 25 Sep 2013)

Human populations have experienced dramatic growth since the Neolithic revolution. Recent studies that sequenced a very large number of individuals observed an extreme excess of rare variants, and provided clear evidence of recent rapid growth in effective population size, though estimates have varied greatly among studies. As medical applications drove the datasets therein, all studies were based on protein-coding genes, in which variants are also impacted by natural selection. In this study, we introduce targeted sequencing data for studying recent human history with minimal confounding by natural selection. We sequenced putatively neutral loci that are very far from genes and that meet a wide array of additional criteria. As population structure also skews allele frequencies, we sequenced a sample of relatively homogeneous ancestry by first analyzing the population structure of 9,716 European Americans. We employed very high coverage sequencing to reliably call rare variants, and fit an extensive array of models of recent European demographic history to the site frequency spectrum. The best-fit model estimates ~3.4% growth per generation during the last ~140 generations, resulting in a population size increase of two orders of magnitude. This model fits the data very well, largely due to our observation that assumptions of more ancient demography can impact estimates of recent growth. This observation and results also shed light on the discrepancy in demographic estimates among recent studies.