Original article from SCIENCE

When humans started to tame dogs, cats, sheep, and cattle, they may have continued a tradition that started with a completely different animal: us. A new study—citing genetic evidence from a disorder that in some ways mirrors elements of domestication—suggests modern humans domesticated themselves after they split from their extinct relatives, Neanderthals and Denisovans, approximately 600,000 years ago.

“The study is incredibly impressive,” says Richard Wrangham, a biological anthropologist at Harvard University who was not involved in the new work. It’s “a really beautiful test,” he adds, of the long-standing idea that humans look so different from our primate ancestors precisely because we have become domesticated.

Domestication encompasses a whole suite of genetic changes that arise as a species is bred to be friendlier and less aggressive. In dogs and domesticated foxes, for example, many changes are physical: smaller teeth and skulls, floppy ears, and shorter, curlier tails. Those physical changes have all been linked to the fact that domesticated animals have fewer of a certain type of stem cell, called neural crest stem cells.

Modern humans are also less aggressive and more cooperative than many of our ancestors. And we, too, exhibit a significant physical change: Though our brains are big, our skulls are smaller, and our brow ridges are less pronounced. So, did we domesticate ourselves?

Giuseppe Testa, a molecular biologist at University of Milan in Italy, and colleagues knew that one gene, BAZ1B, plays an important role in orchestrating the movements of neural crest cells. Most people have two copies of this gene. Curiously, one copy of BAZ1B, along with a handful of others, is missing in people with Williams-Beuren syndrome, a disorder linked to cognitive impairments, smaller skulls, elfinlike facial features, and extreme friendliness.

To learn whether BAZ1B plays a role in those facial features, Testa and colleagues cultured 11 neural crest stem cell lines: four from people with Williams-Beuren syndrome, three from people with a different but related disorder in which they have duplicates instead of deletions of the disorder’s key genes, and four from people without either disorder. Next, they used a variety of techniques to tweak BAZ1B’s activity up or down in each of the stem cell lines.

That tweaking, they learned, affected hundreds of other genes known to be involved in facial and cranial development. Overall, they found that a tamped-down BAZ1B gene led to the distinct facial features of people with Williams-Beuren syndrome, establishing the gene as an important driver of facial appearance.

When the researchers looked at those hundreds of BAZ1B-sensitive genes in modern humans, two Neanderthals, and one Denisovan, they found that in the modern humans, those genes had accumulated loads of regulatory mutations of their own. This suggests natural selection was shaping them. And because many of these same genes have also been under selection in other domesticated animals, modern humans, too, underwent a recent process of domestication, the team reports today in Science Advances.

Wrangham cautions that many different genes likely play a role in domestication, so we shouldn’t read too much evolutionary importance into BAZ1B. “What they’ve zeroed in on is one gene that is incredibly important … but it’s clear there are going to be multiple other candidate genes.”

William Tecumseh Fitch III, an evolutionary biologist and cognitive scientist at the University of Vienna, says he is skeptical of “precise parallels” between human self-domestication and animal domestication. “These are processes with both similarities and differences,” he says. “I also don’t think mutations in one or a few genes will ever make a good model for the many, many genes involved in domestication.”

As for why humans might have become domesticated in the first place, hypotheses abound. Wrangham favors the idea that as early people formed cooperative societies, evolutionary pressures favored mates whose features were less “alpha,” or aggressive. “There was active selection, for the very first time, against the bullies and the genes that favored their aggression,” he adds. But so far, “Humans are the only species that have managed this.”