As the earliest humans migrated through Africa and into Europe long before writing was invented, they didn't leave accounts of their travels. But their story is inscribed, at least partially, in another form: the DNA of their descendants. An unprecedented scan of DNA of three existing African hunter-gatherer populations has now filled in some chapters of that prehistoric tale. The findings hint at new disease threats, the beginnings of agriculture, the reason for Pygmies' short stature, and intermarriage with an unknown species.
A vast amount of genetic information from people around the world is available for scientists wondering how humans got to be the way we are. "But comparatively few studies have focused on populations in Africa, even though Africa is the ancestral home of all humans," says geneticist Sarah Tishkoff of the University of Pennsylvania. So she and postdoc Joseph Lachance, along with a multinational team, sequenced the DNA of three hunter-gatherer groups living in Africa today: the Hadza and Sandawe from Tanzania and the Pygmies from Cameroon, some of the most ancient lineages in the world. These groups have long tantalized anthropologists. All have remained hunter-gatherers, but the Sandawe have intermarried with agrarian peoples and forayed into agriculture; they also have light skin. The dark-skinned Hadza, by contrast, have largely kept to themselves, though living in a similar environment only 150 kilometers away from the Sandawe. And the Pygmies, who live in dense jungle habitat, have remained some of the smallest people on the planet, with adult males seldom topping 1.5 meters.
In the new study, which appears in Cell today, the researchers scrutinized the DNA of five individuals from each group, scanning each genome an average of 60 times. The researchers were looking for telltale variants in the genetic code that could help explain differences between individuals and populations. They turned up over 13.4 million genetic variants, 3 million of which had never before been seen in humans. Among them were sharp differences between the three groups in genetic regions involved in smell and taste—suggesting that each population's senses had adapted to the new smells and foods they encountered. Other characteristic patterns of variants included genes involved in immune system activity and the fat content of breast milk. A group of variants unique to the Hadza spanned the DNA encoding for a cannabinoid receptor, a cell surface protein that responds to tetrahydrocannabinol—the active ingredient in marijuana—which is intriguing because Tishkoff's team observed that the Hadza smoke large amounts of marijuana. The three populations also had distinctive variants around genes that produced blood compounds involved in injury repair.
The team also found a new clue as to why Pygmies are so short. In a previous study of Pygmy genomes, Tishkoff and colleagues had found variants in genes involving human growth factor, which the pituitary gland produces to regulate height. The new study turned up a Pygmy-specific cluster of 44 variants in a gene called HESX1, which is turned on in embryonic development and controls the growth of the pituitary itself. Mutations in this gene result in a pituitary disorder resulting in short stature, but those mutations have not been seen before in Pygmies. The 44-variant cluster, on the other hand, doesn't appear in published genomic scans of non-Africans; the fact that it's common in Pygmies suggests that it may be beneficial.
Exactly how these genetic variants help populations is a mystery, but the fact that each group has them in distinctive patterns is strong evidence that they're involved in adaptation, according to human evolutionary biologist Mary Ellen Ruvolo of Harvard University. She says the study opens up new challenges for biologists to figure out what the variants do. For example, the fact that variants involved in taste and smell differed among the three groups suggests that those variants played a key role in adapting to local diets. "The wound healing genes are intriguing, too," Ruvolo says. "Wouldn't we all benefit from the same degree of healing? Or can some people heal better than others?"
What has most intrigued some researchers, however, is that the study found genetic evidence that all three groups had intermingled sexually with an unknown, older species—possibly an African equivalent of the Neanderthal species in Europe. Not only did the Hadza, Sandawe, and Pygmy people all have significant lengths of DNA from this unknown species, but the union happened at about the same time as European humans were hobnobbing with Neanderthals—tens of thousands of years ago. Tishkoff notes that scientists can't count on finding a fossil specimen of this mysterious species, let alone extracting usable DNA for analysis, but she predicts that genetic methods such as those employed in the new study may help identify this unknown African forebear.
"This study sets the standard for future research into admixtures between humans and earlier species," says anthropological geneticist Mark Shriver of Pennsylvania State University, University Park. Identifying nonhuman ancestors helps us understand our origins in more ways than one, Shriver says. For example, previous research has suggested that modern humans may have received large amounts of immune-system genes by mating with Neanderthals; other human traits may be direct gifts from additional hominin species, Shriver says.