Patterns of deleterious variation between human populations reveal an unbalanced load

Abstract

Each human individual carries ∼30–60 de novo mutations that arose in the germ line of his or her parents (1). At the population level, the result is a massive influx of new mutations every generation, whose evolutionary trajectory is shaped by the joint effects of stochastic and deterministic evolutionary forces. Indeed, considerable information about human history, including changes in population size, structure, and timings of major diasporas, is embedded in extant patterns of neutral genetic variation (2). For example, genetic data from global human populations show a striking gradient of declining genetic diversity with distance from Africa, which has been attributed to serial founder effects associated with the Out-of-Africa migration and subsequent global expansion (3–5). However, in contrast to neutral variation, considerably less is known about geographic patterns of deleterious variation, the fate of which is governed by both random genetic drift and purifying selection. In PNAS, Henn et al. (6) address this question by performing whole-genome sequencing of 54 individuals from seven geographically diverse populations. The authors show that differences in demographic history among populations have influenced patterns of deleterious mutations in a manner predicted by a model of serial founder effects during geographic range expansions (Fig. 1). In addition to revealing new insights into the interaction between selection and demography during recent human evolution, the study quantifies within- and between-population variation in mutational burden, with implications for predicting individual disease risk.