Modeling European demographic history using neutral genomic regions

Neutral genomic regions refine models of recent rapid human population growth

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. [. . .]

The best-fit model points to Europeans having experienced recent growth from an effective population size of about 4-7 thousand individuals as recently as 120--160 generations (3000--4000 years) ago. Growth over the last 3000-4000 years is estimated at an average rate of about 2--5% per generation, resulting in an overall increase in effective population size of two orders of magnitude.

[. . .] Motivated by archeological evidence of growth starting with the Neolithic revolution ~10,000 years ago and accelerating in the Common Era, we considered models that allow for acceleration of the rate of growth, but none supported such acceleration. One recent model considered two separate epochs of exponential growth (21). The first captures a slow recovery from the Eurasian population bottleneck ~23,000 years ago, with a weak growth rate of 0.3% that leads to an Ne of only 9208. This is similar to the instantaneous recovery from the population bottleneck in other models (16), rather than capturing recent rapid growth. Thus, to date no recent acceleration in the rate of growth that is along the lines proposed by archeological evidence has been observed in genetic data. Power calculations showed that our data size and modeling framework should be able to capture such an acceleration in growth in over 60% of cases. One explanation of our modeling not capturing two separate epochs of growth, other than limited statistical power, is that effective population size increases extremely slowly with the census population size, at least initially. While several factors contribute to these phenomenon, the particular increase in census population size with the Neolithic revolution has been accompanied by changing social structure that has led to increased variability in reproductive success; the advent of agriculture led to differential accumulation of richness, more notably in males, resulting in differential access to females compared to a hunter-gatherer life style (45). Increased variance in reproductive success results in relatively decreased effective population size. Perhaps jointly with other population processes, this social shift can explain either a lack of growth in effective population size initially or a milder one, which we have reduced power to capture, and which can lead to our models only capturing the more recent and more rapid growth.

In conclusion, we presented refined models of the recent explosive growth of European populations. These models can inform studies of natural selection (46, 47), the architecture of complex diseases, and the methods that should best be used for genotype-phenotype mapping. We hope that our models and the public availability of our NR dataset will facilitate additional such studies. Importantly, however, models of recent demographic history are still limited to Europeans (19-21) and African Americans (21), and there is a need to extend them to additional populations. As the vast majority of rare variants are population-specific (31, 48, 49), such extended models will also facilitate better consideration of the replicability of genome-wide association studies results across populations.