How natural selection really shaped humanity

HUMANS HAVE never been immune from the pressures of natural selection. Throughout the history of the species circumstances have arisen to give individuals with certain beneficial mutations an advantage over their peers, allowing their valuable genetic variants to spread among a population. Still, the emergence and rapid spread of such variants—known as strong directional selection—was thought to have been a rare occurrence in human evolution. A new study, published in Nature on April 15th, however, reveals it has played a much more influential role.

The dynamics of evolutionary biology have historically been hard to extract from ancient DNA. Small sample sizes are partly to blame, with general conclusions about human adaptation hard to draw from a handful of (often poorly preserved) fragments. Another complication is that sustained genetic variation does not emerge exclusively as a result of natural selection. Genetic mutations can also propagate by chance or through mixing between populations. Sorting the genetic wheat from the chaff many thousands of years after the fact is a challenging task.

To overcome these limitations Ali Akbari and David Reich, a pair of geneticists from Harvard University, developed a new statistical toolkit to use on collections of ancient DNA samples. The researchers hoped it could make sufficiently detailed comparisons between pairs of samples in a collection to distinguish signatures of directional selection from those of non-adaptive mutations.

The researchers then applied their tools to the genetic data of 15,836 ancient individuals of West Eurasian ancestry as well as 6,438 modern humans. The dataset spanned 18,000 years and included new data for 10,016 ancient genomes, representing a doubling of the global pool of ancient DNA data and a 14-fold increase in sample size compared with previous studies searching for natural selection.

The results of the analysis surprised even the authors. Until now, only 21 incidences of directional selection have been found in humans in the past 11,000 years. The new paper, however, identifies 479 gene variants as highly likely to have emerged as a result of natural selection over the same period. That suggests directional selection was pervasive across West Eurasia in recent millennia. “It’s an analytical tour de force,” says Pontus Skoglund, a geneticist at the Francis Crick Institute, who was not involved in the study.

Some of the most intriguing findings emerged when Drs Akbari and Reich focused on variations arising in individual genes. One genetic signature that they focused on, which helps the body identify pathogens, is also associated with an increased susceptibility to coeliac disease. Their analysis suggests that this signature, which is found in roughly one in five of their modern-day samples, was almost absent until around 4,000 years ago. Its emergence may not, as had been previously thought, have been driven by the spread of agriculture, which happened long before.

Another hypothesis they suggest may be wrong concerns genes associated with a higher risk of developing cystic fibrosis, which some have speculated emerged because of the resistance to cholera it granted carriers. Drs Akbari and Reich found no indication of selection for these genes during the period that cholera is thought to have been endemic in West Eurasia, weakening the case for such a connection.

Co-ordinated shifts across collections of genes can also influence more complex traits. The researchers identified 44 signatures of directional selection across such gene groups. They found that genes associated with type 2 diabetes in modern-day humans were selected against, for example, as were those linked to psychiatric conditions such as schizophrenia and bipolar disorder.

Strong directional selection, pervasive though it may be, does not operate at a constant rate. The researchers found that such instances appear to have dramatically intensified for West Eurasians during the Holocene, beginning roughly 11,700 years ago, perhaps because of changing lifestyles following the rise of agriculture. In other populations exposed to different sets of circumstances, the genetic history may well be very different. ■