Ancient DNA from 22,000 Genomes Reveals Hundreds of Recent Human Evolutionary Shifts in Europe and Near East

Around 4,000 years ago, while the Minoans were building on Crete and the Neo-Sumerian Empire held sway in Mesopotamia, something was also shifting in the bodies of the people living there. Two DNA variants linked to celiac disease became sharply more common across populations in Europe and the Near East. That finding comes from a study published last week in Nature, and it is one of hundreds the paper documents.

The work was led by scientists at Harvard University. They compared the complete genomes of about 22,000 people: 10,000 ancient genomes that had never been studied before, 6,000 that had been published earlier, and 6,000 from modern individuals. The samples came from countries stretching from Iceland to Spain, Russia, Iran and Israel. The question was how natural selection has shaped human biology over the last 10,000 years. Natural selection here means a version of a gene that proves advantageous enough for survival and reproduction to spread, whether it relates to a disease, red hair or a blood type.

Until now, only 21 genetic shifts of this kind were known. David Reich, the study's senior author and a Harvard geneticist, told The Times of Israel in a video interview that the near-live view is what makes the work powerful: it lets researchers watch evolution in action rather than study only the scars it leaves on modern variation. He now counts almost 500 genome positions with clear evidence of adaptation, compared with about 20 in the earlier literature. He added that probably several thousand more would appear if the threshold for certainty were lowered.

The data took years to assemble. Reich said that extracting DNA from human remains became possible only in 2010. Studying history needs only one or a few samples per population, but studying evolution needs many. So his lab and others spent the last decade, in his words, industrializing the production of ancient DNA, using robots to extract, clean and prepare it for sequencing, plus uniform computational methods for analysis. About 270 archaeologists supplied samples, on the understanding that research touching on the history angle would be shared later. Reich says the result doubled the data in the whole field of ancient DNA and tripled what was available for West Eurasia. The team used only samples with reliable, fairly precise dating, from radiocarbon, soil-layer placement, or both, and excluded those with less clear chronology.

The harder problem was separating selection from everything else. Migrations and mixtures of groups also change how common a variant is. Ali Akbari, the lead author and a senior staff scientist in the Reich Lab, devised the strategy. The model compared each genome with the other 22,000 to measure relatedness. Human genomes are about 99.9 percent identical, Reich explained, so of roughly 3 billion letters there may be about 3 million differences. The system examined about 10 million variable letters and tested whether time alone helped predict how they changed.

The celiac result runs against intuition. One might expect the variants to have faded as people began eating wheat, Reich said, but they became more common. He does not know why, and suggests they probably protected against some other disease. Tuberculosis showed a different pattern. One variant, the most important risk factor for serious TB, was strongly selected to increase between 6,000 and 2,000 years ago, then strongly selected against. Reich called his explanation speculative: once TB became widespread, carrying the variant turned costly, though it may earlier have protected against another infection. The study also traced variants tied to multiple sclerosis, hemochromatosis, bipolar disease and Crohn's disease, and to traits such as red hair, light skin and blood types.

The authors released an open database where researchers can look up any position in the genome and see which variants occur there. Reich said few Jewish individuals were in the sample, partly because Jews were typically buried in distinct cemeteries, making Jewish DNA unlikely to turn up in non-Jewish burials. The team also did not compare regions within West Eurasia, including ancient DNA from the land of Israel. He called that an important direction and the current study only the beginning. Larger samples should yield more discoveries, and he hopes to run similar studies in East Asia and among Native Americans, and perhaps on animal DNA.