  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. All these 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 loci very far from genes
that meet a wide array of additional criteria such that mutations in these loci
are putatively neutral. 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.
