the emergence of modern humans was.
We carry genes from our ancestors' encounters
with ancient people like the Neanderthals,
but the Neanderthals already carried
some modern human genes
from even earlier encounters
interbred many times throughout
Eurasia and Africa,
and the genetic flow
went both ways.
With every fossil discovered, with every DNA analysis performed, the story gets more complex:
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.
It's another to provide concrete details about when and where those couplings occurred.
You think you're just looking at a Neanderthal,
but you're actually looking at
a mixture of Neanderthal and modern human.
Cold Spring Harbor Laboratory
Evidence of interbreeding during any migrations before then, or
during events that transpired earlier within Africa, has been
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.
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% 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% of the genome of people in Papua New Guinea and Australia.
Nor does it allow researchers to test specific hypotheses
about how that interbreeding unfolded.
But discerning interbreeding that occurred between those periods, from events,
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.
and his team at Cold Spring Harbor Laboratory campus
searched through contemporary and fossil DNA
for signs of gene flow from modern humans
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.
Using one such new technique, first in 2016 and then again in a preprint posted earlier this summer, Siepel and his team found that around 3% of Neanderthal DNA - and possibly as much as 6% - came from modern humans who mated with the Neanderthals more than 200,000 years ago.
The same group who gave rise to modern humans throughout the world also furnished Neanderthals with (at least a little) more DNA than the Neanderthals would later give them.
Such a high level of genetic admixture, he added,
And yet the methods in general use had not.
To Hawks, the omission suggests that there may be a lot more shared genetic material still to find even if it can't yet be quantified accurately.
More advanced techniques may change that.
Modern humans were thought to have evolved in Africa after the departure of Neanderthals and Denisovans, and to have remained on the continent until their well-known out-of-Africa diaspora 60,000 years ago.
But recently, fossil evidence has indicated otherwise:
In fact, with that piece of skull, archaeologists may have stumbled across a possible member of the long-ago exodus that Siepel and his team inferred in their genomic study.
The fossil, which was classified as Neanderthal when it was unearthed in Greece in the 1970s, was analyzed last month by the paleoanthropologist Katerina Harvati of the University of Tübingen and her colleagues.
Structurally, it looked somewhat like a modern human skull, but it was estimated to be about 210,000 years old - supposedly too old to be modern at that location.
(Because the structural similarities to modern skulls show up in reconstructive models of the Greek fossil, the conclusion is controversial and will probably continue to be until DNA can be recovered for a genetic study to confirm it.)
The Apdima 1 skull fossil found in Greece
has many modern structural features
but is 210,000 years old - too ancient
to be from any of the modern humans
who left Africa only 60,000 years ago.
It may have come from a hypothesized
earlier exodus that left no survivors.
©️ Katerina Harvati, University of Tübingen
Now the DNA evidence seems to back up this revised migration narrative as well.
Humans have been continuously evolving through the mixing of varied populations for hundreds of thousands of years.
(In fact, Aylwyn Scally posits that our species did not originally evolve from a single population in Africa, but rather from many interconnected populations spread out across the continent.)
What is curious is that the only migration that seems to have left modern human descendants in Europe and Asia was the one from 60,000 years ago.
The groups that migrated earlier apparently all died out or got absorbed into Neanderthal or other ancient populations.
This could mean, he said, that,
Furthermore, when the Neanderthals then interbred with modern humans during later migrations, perhaps some of that DNA got mixed back into the modern human genome, embedding older signals of Homo sapiens history into the genetic material of individuals alive today.
According to Siepel's analysis, that sort of nested mixing seems to have been exactly what happened with the Denisovans.
When the team looked at the Denisovan genome, they found fragments of DNA in it from an even earlier hominin, vestiges of some population whose own genome has not been found or sequenced.
It might have been Homo erectus, which split off from the ancestors of modern humans and spread across Eurasia about 1 million years ago.
The contribution from this unidentified group "was at the limits of our detection power," according to Siepel, because it constituted only about 1% of the Denisovan genome.
During later interbreeding events, tiny pieces of that 1% got passed on to modern humans in Southeast Asia, Papua New Guinea and some parts of East Asia.
A Return to Africa
Serena Tucci, a postdoctoral researcher in Akey's lab, said the work shows
In Siepel's case, that meant testing a vast number of hypotheses by inferring the branching inheritance patterns of various genes.
Other scientists are starting to rely on different probabilistic approaches.
Siepel now hopes to apply his approach to other elusive aspects of history.
He's particularly interested in prehistoric population dynamics on the African continent.
How ancient genetic admixture events affected modern African genomes has been little studied - although a pair of researchers recently reported in PLOS Genetics that humans in Africa interbred with another ancient hominin group both before and after the ancestors of European and Asian populations split off and migrated away.
By the scientists' estimates, DNA from that unknown group now makes up somewhere between 4% and 8% of modern human ancestry.
That said, Siepel's technique could perhaps provide deeper insights into those statistics and what they mean:
Siepel is also using his algorithm to look for signs of natural selection acting on these DNA sequences:
So far, his team has found no evidence for either positive or negative selection in the flow of genes from modern humans into Neanderthals 200,000 years ago, which indicates that,
That's something that can be studied in other species as well: Siepel has already started to look into the forces at work in the speciation of certain birds.
Of course, inferring these population histories is a complicated process.
Sometimes, alternative historical scenarios have basically the same effects on the genomic record, and in those situations, even better methods of genetic analysis will be hard-pressed to squeeze answers out of the data.
Still, he added, we're a long way off from reaching that limit.
Aylwyn Scally agreed.