Scientists Uncover Two Mysterious 'Ghost' Ancestors Hiding in Modern Human DNA

Researchers at the University of California, Berkeley have identified specific regions of the modern human genome inherited from two previously unknown archaic human lineages, estimating when interbreeding with these "ghost" ancestors occurred. The findings, published online July 30 in the journal Science, were made possible by a new computational technique that reconstructs ancient genealogical connections using only present-day human genomes—no ancient DNA required.

The work was led by Yulin Zhang, a graduate student at Berkeley's Center for Computational Biology, and Arjun Biddanda, a postdoctoral researcher at Johns Hopkins University, under the direction of Priya Moorjani, a Berkeley associate professor of molecular and cell biology.

A Ghost Ancestor Shared by All Humans

One of the unknown groups, described by the researchers as a ghost ancestor, interbred with modern humans in Africa more than 50,000 years ago, before the most recent major movement of Homo sapiens out of Africa and into Europe and Asia. DNA inherited from this lineage makes up approximately 1% of the modern human genome—an amount similar to the proportion inherited from Neanderthals.

The ghost lineage separated from the ancestors of modern humans around 800,000 years ago, close to the time when Neanderthals and Denisovans split from one another. However, the ghost population exchanged genes with modern humans at an earlier point than the Neanderthal and Denisovan encounters outside Africa.

"Previous publications suggested that there might be ghost ancestry—ancestry from unknown archaic lineages in modern humans—but they hadn't concluded whether this unknown ancestry is present only in Africans or not, and when this introgression event happened," said Zhang. "We were actually able to find and map genomic locations in modern humans that are from this ghost lineage and show that this ghost ancestry is in all modern humans, not only in Africans."

The ghost ancestry appeared in both African and non-African populations, a widespread distribution indicating that the interbreeding happened before Homo sapiens made their final major migration out of Africa. "We discovered that about 2% of the modern human genome is from archaic hominins," Zhang said. "In the case of the ghost lineage, modern-day Africans and non-African populations both inherited similar amounts of ghost ancestry. Each individual has about 0.5 to 1% of their genome inherited from this ghost lineage."

DNA From a Million-Year-Old Lineage

The researchers also detected genetic material from an even more ancient population, which they call a super-archaic ancestor. This hominin descended from a lineage dating back about 1.8 million years and appears to have interbred with Denisovans in Eurasia, probably more than 200,000 years ago. Denisovans later mixed with Homo sapiens, allowing a small portion of that super-archaic DNA to enter the genomes of modern humans.

"The super-archaic finding is particularly exciting because it reveals genetic contributions from a human lineage that lived over a million years ago, despite the absence of any sequenced DNA from that population," said Biddanda.

The super-archaic genetic signal appeared within sections of Denisovan DNA, suggesting that the ancient lineage first contributed DNA to Denisovans, who later passed a portion of it to modern humans. Denisovan genomes contain an estimated 3% to 5% super-archaic ancestry. Because only some Denisovan DNA entered modern human populations, people alive today inherited only a small fraction of that much older genetic material, according to Moorjani.

Tracing Archaic DNA Without Fossils

Modern humans who left Africa roughly 50,000 years ago encountered Neanderthals and Denisovans in Eurasia and interbred with both groups. Although Neanderthals and Denisovans later disappeared, portions of their genomes survived in their modern human descendants. Scientists uncovered that inheritance by extracting and sequencing DNA preserved in fossils, but the genomes of living people also contained signs of much older episodes of interbreeding that were difficult to investigate because scientists lack sequenced DNA from most other extinct hominins.

To overcome that limitation, Moorjani's team created a technique called TRACE (TRacking Archaic Contributions via ARG Estimation). Instead of relying on ancient remains, TRACE searches for archaic genetic regions using complete genomes from present-day people. The researchers examined genomes from individuals around the world and reconstructed the relationships among DNA segments over many generations—a reconstruction known as an ancestral recombination graph (ARG).

"Genealogies preserve a record of our evolutionary past," said Moorjani. "TRACE reconstructs those histories across the genome. By identifying regions whose ancestry extends unusually far back in time, we can uncover genetic contributions from extinct human populations, even in the absence of ancient DNA."

The team ran TRACE on 503 genomes from the 1000 Genomes Project, spanning people from Europe, East Asia, South Asia, and two African populations, and separately on 92 genomes from Papua New Guinea, Vanuatu, and the Santa Cruz Islands. They also validated the method on simulated genomes where the answer was already known; with no ghost group in the simulation, TRACE reported 0.07% ghost ancestry, far below what it found in real people.

Ancient Interbreeding May Have Helped Humans Adapt

Many of the archaic DNA segments were concentrated in genomic regions connected with immune defenses and metabolism, Moorjani said. The team counted 1,932 spots where ghost DNA is unusually common, compared with 1,155 spots for Neanderthal DNA and 160 for Denisovan. Many of the genes at those spots help fight infection or move fats through the blood, and some help the body distinguish an invader from its own cells.

"This pattern is not entirely surprising," Moorjani said. "Adaptation to new pathogens and food sources has been one of the strongest selective pressures in human evolution. Interbreeding with other human groups introduced new genetic variation, providing additional raw material for natural selection. Beneficial variants could then be retained and spread over many generations."

Notably, the ghost ancestry was detected even in regions previously thought to be intolerant of Neanderthal and Denisovan ancestry. "TRACE allowed us to contextualize how the ancestry segments from these previously uncharacterized hominins are distributed throughout the human genome," Biddanda said. "We found that these contributions are widespread throughout the genome, and ghost ancestry is detected even in regions previously thought to be intolerant of Neanderthal and Denisovan ancestry." At one spot on chromosome 7, ghost DNA appeared in 13.3% of the copies sampled.

A More Interconnected Human History

Together, the findings suggest that early Homo sapiens lived alongside numerous related human groups in Africa and Eurasia during the past million years. These populations were genetically similar enough to have children together, leaving behind lasting biological traces.

"With ancient DNA from Neanderthals and Denisovans and with these new genealogical methods, we are learning that mixture among human populations has been very pervasive across time, and that this is also likely to be true at ancient time scales," said Moorjani. "We often think of human evolution as a branching tree, but new genomic data and analytical methods reveal a much more interconnected history—more like a complex web of populations connected by repeated episodes of migration and mixing."

Scientists still do not know the identities of the ghost and super-archaic populations. However, the estimated dates when they separated from other human lineages overlap with Middle Pleistocene Homo groups living in Africa around 800,000 years ago—including Homo heidelbergensis—and Homo erectus populations living in Eurasia around 1.8 million years ago, respectively.

Moorjani hopes that TRACE will eventually uncover weaker signals from additional unknown populations as global genome databases include a broader and more representative range of human populations. Additional Denisovan genomes would also give researchers more material for comparison, and protein fragments recently recovered from Homo erectus fossils could potentially help reveal the identity of the super-archaic population.

"I think these new computational methods that allow us to reconstruct genealogical relationships are really the next frontier in this field because they are allowing us to uncover hidden episodes from our past without requiring ancient DNA," Moorjani added. She noted that TRACE should also work with other species, "allowing us to also uncover really different patterns across the tree of life."

Other co-authors of the paper are Sarah Johnson of Berkeley's Center for Computational Biology and Colm O'Dushlaine of 54Gene, Inc., in Washington, D.C. The work was funded by the National Science Foundation.