Did human women contribute to Neanderthal genomes over 200,000 years ago?

A new Neanderthal mitochondrial genome supports a remarkable hypothesis – that there was interbreeding with an extremely early migration of African hominins.

Head and shoulders of a sculpted model of a female Neanderthal. Photograph: Alamy

Keeping pace with new developments in the field of human evolution these days is a daunting prospect. It seems as though every few weeks there’s an announcement of exciting new findings from hominin fossils, or the recovery of an ancient genome that significantly impacts our understanding of our species’ history.

The best way to keep up is by regularly revisiting and reassessing a few core questions. When and where did our species first appear? How and where did we migrate? What was our relationship to our (now-extinct) hominin relatives? What evolutionary and cultural factors influenced our histories? How do new findings change the answers to these questions? Are they generally accepted by the relevant community of experts, or are they provisional or controversial?

This month’s challenge is to understand the significance of a recently published Neanderthal mitochondrial genome from a femur that was excavated in 1937 from the Hohlenstein-Stadel (HST) cave site in southwestern Germany. This new genome brings the total number of Neanderthals from whom we have genetic information to eighteen.

The Hohlenstein Stadel cave, north of Langenau, Germany. Photograph: TH. BEUTELSPACHER / HANDOUT/EPA

Reconstructing past population history accurately requires temporal and geographic diversity in sampling. It’s tremendously important. Someday we will have so many archaic genomes sequenced that a new one isn’t a big deal and doesn’t add very much to the panoply. But that day isn’t here yet, and so the recovery of genetic data from each new individual has the potential to make a huge difference in how we understand evolutionary history.

This is the case with the new HST Neanderthal mitochondrial genome, which is strikingly different to all others sequenced thus far – so much so that it nearly doubles the known genetic diversity of Neanderthal populations.

The HST genome may resolve a longstanding point of confusion regarding the evolutionary relationships between modern humans, Neanderthals, and Denisovans. We actually get different histories for the three groups depending on whether we analyze their mitochondrial (maternally inherited) or nuclear (bi-parentally inherited) genomes. Nuclear DNA indicates that Neanderthals and Denisovans were more closely related to one another than to humans, and that the three groups last shared a common ancestor sometime between 765-550,000 years ago. Neanderthals and Denisovans diverged later (probably by 430,000 years ago) into genetically and geographically distinct groups.

However, mitochondrial DNA (inherited exclusively maternally) shows a different pattern: humans and Neanderthals appear to be more closely related to each other, and the Denisovans are a more distant cousin group.

The nuclear DNA story is most likely the correct one, as nuclear genomes give us a much more robust glimpse into the past by allowing us to look at the independent histories of thousands of genetic markers. But why does the mitochondrial DNA disagree?

One explanation for these results is that Neanderthal mitochondrial genomes may actually derive from gene flow with another group of hominins from Africa, ancestral or closely related to modern humans, whose maternal lineages effectively replaced the older Denisovan-like lineages. Indeed, the 430,000 year old hominins from the Sima de los Huesos site in Spain, who physically resemble the ancestors of Neanderthals, have early Neanderthal-like nuclear genomes but more Denisovan-like mitochondrial genomes, suggesting that the early Neanderthal populations had maternal lineages very unlike those found in later populations. If there was gene flow into Neanderthal population from female hominins from Africa, it’s possible that there could have been a complete replacement of the maternal lineages in this population without obscuring the histories reflected in the nuclear genome.

The HST genome has now provided a good chance to test this hypothesis, because it is quite old – about 124,000 years, according to an estimate based on the molecular clock (in contrast to most other published Neanderthal genomes, which are much more recent). HST’s mitochondrial lineage is distinct from all other Neanderthal mitochondrial genomes sequenced thus far, and is basal (very ancient) relative to them. Using this new mitochondrial genome in their analyses, researchers found it was indeed plausible that some hominins may have migrated out of Africa and interbred with Neanderthals sometime between 413,000 and 270,000 years ago, perhaps in the Middle East. This event would have significantly predated the major Out-of-Africa human migration, which is currently thought to have occurred around 75,000 years ago. There is other evidence to suggest that early human populations were much more mobile than we had previously thought, such as the recent classification of hominin fossils in Morocco dating to 300,000 years ago as early “pre-modern” H. sapiens. These data may give indirect support for early small-scale migrations before the major spread of human populations out of Africa.

A reconstruction of a Neanderthal family from Krapina. Photograph: Nikola Solic/Reuters/Corbis

The HST mitochondrial genome adds more important details to our ever-expanding understanding of hominin evolution and allows us to be a bit more confident in one model that resolves seemingly contradictory genetic results. While nuclear DNA from the HST fossil would tell us even more, unfortunately the endogenous Neanderthal DNA in the fossil is not well preserved. Of the ~240,000 unique sequence reads recovered from the femur, only about 1,110 were from the Neanderthal. The rest were from other organisms such as soil bacteria and modern humans. These high contamination and low endogenous DNA levels mean that it will be difficult to obtain a nuclear genome from this bone.

I feel like every time I write about ancient DNA it’s an exercise in expectation lowering, since so few remains ever yield their genetic secrets. So here I want to emphasize that what we have learned about our histories from this single fossil really is remarkable. The brand new editions of textbooks that many of us are planning on using for our courses next term are already completely out of date, and I’m hopeful there are even more surprises to come in the near future. I’m sure I speak for the whole biological anthropology community when I say that we couldn’t be happier about the pace of discoveries these days, even if it does feel overwhelming.