For a brief period in our species’ history, we shared our world with other sapient humans, closely related to us but distinct. We don’t know much about how our ancestors interacted with these other now-extinct hominins, but we know that at least some of those interactions were pretty intimate, because many modern humans now carry traces of DNA from Neanderthals and another ancient hominin group called Denisovans.

Most modern people of European and Asian descent carry between one- and three-percent Neanderthal DNA, and most people of Asian and Oceanian descent carry up to five-percent Denisovan DNA. Because Neanderthals and Denisovans arose outside Africa, the ancestors of modern African people would never have encountered them, although researchers have suggested that a so-far unidentified hominin species in Africa mingled with our ancestors there, so all of us may carry traces of that distant relative as well.

These weren’t isolated incidents. The genetic legacy that many of us now carry is probably the mark of years of sustained contact between two groups. Consistent with that, it now turns out that humans may have had contact with Denisovans not just at one place and time, but two.

Still in our genes

Sharon Browning, a research professor of biostatistics at the University of Washington, Seattle, and her colleagues made the discovery while testing a new method of scanning human DNA for exactly this kind of mixing with now-extinct hominin species like Neanderthals and Denisovans.

One way to do that is to simply compare the genomes side by side and look for points that seem to match. We can make that kind of comparison with Neanderthals and Denisovans because scientists have sequenced genomes for both species. But for researchers looking for traces of the unknown African hominin species mentioned above (or any other species without a sequenced genome), that obviously won’t work.

Scientists can also use a statistical method to look for groups of genes that seem out of place. It works because genes naturally collect mutations over time; most of them are small things that don’t make any difference, although others can eventually affect our characteristics through natural selection. Humans and Denisovans had been separated from their last common ancestor for a long time when we met again, so our genomes had been busy acquiring their own distinct sets of mutations. The statistical method scans a human genome to look for groups of genes that seem to have lots of mutations that don’t show up in the rest of the population. Those get flagged as potentially having come from interbreeding with another hominin species.

Browning and her colleagues developed a new version, which works at a larger scale than the method already being used. They tested it on 5,639 human genome sequences of people from Europe, Asia, the Americas, and Oceania; in case you’re wondering where to get several thousand complete human genomes, Browning and her colleagues got these from the UK10K Project, 1000 Genomes Project, and the Simons Genome Diversity Project.

When they found genetic sequences that looked potentially Denisovan, they compared them to the only Denisovan genome sequence we have, which came from a 30,000- to 50,000-year-old fossil found in a cave in the Altai Mountains of Siberia.

Not once, but twice

People of South Asian and Oceanian descent had different sets of Denisovan genes from people of East Asian descent. The East Asian genomes in the study carried genes that were closely related to the Altai specimen, but they also carried some that weren’t. Meanwhile, the South Asian and Oceanian genomes only carried genes that weren’t related to the Altai Denisovan. The best explanation is that Denisovans and humans interbred twice in our history, not just once, and that the Denisovans had already split into distinct populations.

Here’s one possible scenario: some time after the first Denisovans reached Eurasia, one group gradually moved northward, eventually reaching Siberia. Another group moved south, across South Asia and into the islands of Oceania. By 40,000 to 60,000 years ago, modern humans were migrating into the same region, where they met the southern Denisovan branch and co-existed long enough to interbreed. Modern people of South Asian and Papuan ancestry still carry the genetic traces of that interaction.

Modern people of East Asian ancestry carry the same genetic traces, which means their ancestors hadn’t yet split off from South Asian populations when we met Denisovans for the first time. But they also have a set of Denisovan genes more closely related to the Altai fossil, which South Asian and Oceanian genomes don’t have. At some point after the split, the ancestors of today’s East Asian populations may have met the northern branch of Denisovans, which had been separated from its southern relatives long enough for its genes to start to look different. They, too, interacted and interbred for a while, and that, too, left its genetic mark for Browning and her colleagues to find.

We don’t know exactly when either of those events happened, and researchers can’t actually be sure of the order they happened in. Further research might one day shed some light on that, and that’s part of what Browning and her colleagues could accomplish by applying their method to more human genome sequences from around the world. They also want to look for other instances of interbreeding, either with Neanderthals and Denisovans or with potential African hominins.

“Previous studies have found suggestive evidence of admixture from unidentified hominin species, but further work is needed to look into this more deeply,” said Browning. “Any Homo lineage that overlapped in time with modern humans is a candidate.”

In other words, our family tree may be a lot more complicated than we think. If researchers do find evidence of even more genetic mingling with other early hominins, “It would tell us about the complexity of human history and also tell us that perhaps we weren’t so different from the other hominins,” said Browning.

Cell, 2017. DOI: 10.1016/j.cell.2018.02.031 (About DOIs).