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How Neanderthal DNA might have shaped some human brains

CT scans of a neanderthal cranium (l) and a modern human (r) rotating on a black background

Neanderthal skulls (left) are more elongated than modern-human skulls.Credit: Philipp Gunz

No human has the brain of a Neanderthal — but some have hints of its shape.

The brain shape of some people with European ancestry is influenced by Neanderthal DNA acquired through interbreeding tens of thousands of years ago, researchers report on 13 December in Current Biology1.

These DNA variants seem to affect the expression of two genes in such a way as to make the brains of some humans slightly less round, and more like the Neanderthals’ elongated brains.

“It’s a really subtle shift in the overall roundedness,” says team member Philipp Gunz, a palaeoanthropologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “I don’t think you would see it with your naked eye. These are not people that would look Neanderthal-like.”

The Neanderthal DNA variants alter gene expression in brain regions involved in planning, coordination and learning of movements. These faculties are used in speech and language, but there is no indication that the Neanderthal DNA affects cognition in modern humans.

Instead, the researchers say, their discovery points to biological changes that might have endowed the human brain with its distinct shape.

Changing brains

Earlier this year, Gunz and two colleagues determined that the rounded brain shape of modern humans evolved gradually, reaching its current appearance between 35,000 and 100,000 years ago2. The earliest human fossils from across Africa, dating to around 200,000–300,000 years ago, have large yet elongated brains. “There really is something going on in the brain that changes over time in the Homo sapiens lineage,” says Gunz.

Given that brains don’t fossilize well, looking at how Neanderthal DNA affects human biology is one of the only ways to study differences between the species, says Tony Capra, an evolutionary geneticist at Vanderbilt University in Nashville, Tennessee. “We’re never going to be able to dig up a Neanderthal brain intact and compare it to our brain,” he says.

So the team set out to identify DNA variants that contributed to humans’ rounded brains. They hypothesized that some Neanderthal variants — which all humans with Eurasian ancestry carry — might affect H. sapiens brain shape and make it more elongated.

They first analysed brain scans from 4,468 people of European ancestry, and quantified their overall roundedness. The researchers then tested whether any of about 50,000 Neanderthal DNA variants known to occur in some modern humans were associated with difference in their brain shape.

They pinpointed variants near two genes. The variants don’t alter the shape of the proteins those genes encode — but rather, where in the brain they are made.

Neanderthal variants near a gene called UBR4, which has a role in making neurons, reduce that gene’s expression in deep brain structures called the basal ganglia.

People with a Neanderthal variant near a gene called PHLPP1, which is involved in building the fatty sheaths that insulate nerves, have greater expression of that gene in their cerebellums.

Important function

Cedric Boeckx, a neuroscientist at the Catalan Institute for Research and Advanced Studies in Barcelona, Spain, is intrigued by the brain regions in which expression of these genes is altered, which have previously been linked to human cognition, and to either the absence of or suppression of Neanderthal genes.

For example, a 2017 study found that the expression of Neanderthal genes tends to be suppressed in the basal ganglia and cerebellum3, suggesting that the human versions of the genes are important to brain function.

Speech and tool use are also likely to depend on exquisite motor control underpinned by these regions, notes Simon Fisher, a neurogeneticist at the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who led the latest study.

Fisher co-discovered a gene implicated in language, FOXP2, that influences brain circuits in the basal ganglia and cerebellum. A study in 2014 found that FOXP2 lies in a large swathe of the human genome that contains no Neanderthal variants.4

Yet the researchers say there is no evidence that the variants they identified in the new study affect language or any trait other than brain shape.

And, both Fisher and Boeckx say that many more genes, active in different parts of brain, probably also affect the brain’s roundedness. “We don’t see this as something where this is a single gene that magically changed brain shape,” Fisher says.

Next, his team plans to look for more variants that affect this trait in the UK Biobank database, which is gathering brain scans and genome data for 100,000 people. “We need to go and find more of these genes,” he says.



  1. 1.

    Gunz, P. et al. Curr. Biol. (2018).

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  2. 2.

    Neubauer, S., Hublin, J.-J. & Gunz, P. Sci. Adv. 4, eaao5961 (2018).

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    McCoy, R. C., Wakefield, J. & Akey, J. M. Theory 168, 916-927.e12 (2017).

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    Vernot, B. & Akey, J. M. Science 343, 1017–1021 (2014).

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