Humans today are mosaics, our genomes rich tapestries of interwoven ancestries. With every fossil discovered, with every DNA analysis performed, the story gets more complex: We, the sole survivors of the genus Homo, harbor genetic fragments from other closely related but long-extinct lineages. Modern humans are the products of a sprawling history of shifts and dispersals, separations and reunions—a history characterized by far more diversity, movement, and mixture than seemed imaginable a mere decade ago.

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research develop­ments and trends in mathe­matics and the physical and life sciences.

But it’s one thing to say that Neanderthals interbred with the ancestors of modern Europeans, or that the recently discovered Denisovans interbred with some older mystery group, or that they all interbred with each other. It’s another to provide concrete details about when and where those couplings occurred. “We’ve got this picture where these events are happening all over the place,” said Aylwyn Scally, an evolutionary geneticist at the University of Cambridge. “But it’s very hard for us to pin down any particular single event and say, yeah, we’re really confident that that one happened — unless we have ancient DNA.”

“You think you’re just looking at a Neanderthal, but you’re actually looking at a mixture of Neander­thal and modern human.” Adam Siepel, Cold Spring Harbor Laboratory

The events that do get pinned down therefore tend to be relatively recent, starting with the migration of modern humans out of Africa 60,000 years ago, during which they interacted with hominin relatives (like the Neanderthals and Denisovans) they met along the way. Evidence of interbreeding during any migrations before then, or during events that transpired earlier within Africa, has been elusive.

Now that’s starting to change. In part because of greater computational power, “we’re starting to see the next wave of methods development,” said Joshua Akey, a professor of genomics at the Lewis-Sigler Institute for Integrative Genomics at Princeton University. “And that’s allowing us to start making new inferences from the data … that the previous generation of methods couldn’t make.”

As scientists peer further back in time and uncover evolutionary relationships in unprecedented detail, their findings are complicating the narrative of human history and rescuing some formerly missing chapters from obscurity. Clues are emerging about the unexpected influence of gene flow from ancient hominins on modern human populations before the latter left Africa. Some researchers are even identifying the genetic contributions modern humans might have made to those other lineages, in a complete reversal of the usual scientific focus. Confusing and intertwined as these many effects can be, all of them shaped humanity as we now know it.

Old Humans, New Tricks

When researchers first recovered DNA from Neanderthal bones, the available techniques for making sense of it were powerful but relatively simple. Scientists compared ancient and modern sequences, tallied up shared sites and mutations, and conducted bulk statistical analyses. That’s how they discovered in 2010 that Neanderthal DNA makes up approximately 2 percent of the genome of people today of non-African descent, a result of interbreeding that occurred throughout Eurasia beginning 50,000-60,000 years ago. That’s also how they discovered that Denisovan DNA makes up approximately 3 percent of the genome of people in Papua New Guinea and Australia.

“But that kind of very simple approach isn’t very good at sorting out the complexity” of how those lost populations interacted, said John Hawks, a paleoanthropologist at the University of Wisconsin, Madison. Nor does it allow researchers to test specific hypotheses about how that interbreeding unfolded.

Population geneticists could backtrack through the DNA data to identify common ancestors from hundreds of thousands of years ago, and they could detect recent incidents of gene flow from the past few tens of thousands of years. But discerning interbreeding that occurred between those periods, from events “old enough not to be recent but young enough not to be ancient,” Hawks said, “that actually takes an extra trick.” That’s because the more recent events smear their footprints over the older ones; the DNA sequences left behind from those older events are so fragmented and mutated that they are difficult to recognize, and even more difficult to label with a date and location.

Adam Siepel and his team at the Cold Spring Harbor Laboratory searched through contemporary and fossil DNA for signs of gene flow from modern humans into Neanderthals. Constance Brukin/CSHL

Adam Siepel, a quantitative biologist at Cold Spring Harbor Laboratory in New York, and his colleagues decided to focus on such gaps in the narrative. They were particularly interested in looking for signs of gene flow from modern humans into Neanderthals. That flow of genetic information is harder to study than the reverse, not only because of how long ago it happened, but also because there are fewer genomes to refer to: Think of all the present-day genomes at researchers’ disposal, versus the handful of Neanderthal genomes left intact, or the single genome recovered from Denisovan remains. The challenge again prompted the need for new methods.