Neandertal genes give clues to human brain evolution

December 13, 2018

A distinctive feature of modern humans is our round (globular) skulls and brains. On December 13, in the journal Current Biology, researchers report that present-day humans who carry particular Neandertal DNA fragments have heads that are slightly less rounded, revealing genetic clues to the evolution of modern brain shape and function.

"We captured subtle variations in endocranial shape that likely reflect changes in the volume and connectivity of certain brain areas," says Philipp Gunz, a paleoanthropologist at the Max Planck Institute for Evolutionary Anthropology, who co-led the study with Amanda Tilot of the Max Planck Institute for Psycholinguistics.

"Our aim was to identify potential candidate genes and biological pathways that are related to brain globularity," says Amanda Tilot.

To tightly focus their search, they took advantage of the fact that living humans with European ancestry carry rare fragments of Neandertal DNA buried in their genomes, as a result of interbreeding between Neandertals and the ancestors of modern Europeans. Different people carry different fragments, which are scattered through the genome.

Gunz, Tilot, and colleagues analyzed cranial shape and identified stretches of Neandertal DNA in a large sample of modern humans, relying on MRI brain scans and genetic information for about 4,500 people. Based on computed tomographic scans, they computed the endocranial shape differences between Neandertal fossils and modern human skulls. They used this contrast to assess endocranial shape in thousands of MRI brain scans of living people.

They used information from sequenced genomes of ancient Neandertal DNA to identify Neandertal DNA fragments in living humans on chromosomes 1 and 18 that correlated with reduced cranial roundness. These fragments contained two genes already linked to brain development: UBR4, involved in the generation of neurons, and PHLPP1, involved in the development of myelin insulation around nerve cell projections.

"We know from other studies that completely disrupting UBR4 or PHLPP1 can have major consequences for brain development," says senior author Simon Fisher (@ProfSimonFisher), a geneticist at the Max Planck Institute for Psycholinguistics. "Here we found that, in carriers of the relevant Neandertal fragment, UBR4 is slightly down-regulated in the putamen. For carriers of the Neandertal PHLPP1 fragment, gene expression is slightly higher in the cerebellum, which would be predicted to have a dampening effect on cerebellar myelination."

The putamen--part of a network of brain structures called the basal ganglia--and the cerebellum are thought to be important in movement.

"Both brain regions receive direct input from the motor cortex and are involved in the preparation, learning, and sensorimotor coordination of movements," says Gunz. "The basal ganglia also contribute to diverse cognitive functions, in memory, attention, planning, skill learning, and potentially speech and language evolution."

The researchers stress that the effects of carrying these rare Neandertal fragments are subtle and only detectable in a very large sample size.

"The Neandertal variants lead to small changes in gene activity and only push people slightly towards a less globular brain shape," says Fisher. "This is just our first glimpse of the molecular underpinnings of this phenotype, which is likely to involve many other genes."

The researchers are preparing to scale up their approach and apply it to tens of thousands of people. That will enable them to carry out a fully genome-wide screen to reveal additional genes associated with cranial roundness and other biological characteristics.

"The interdisciplinary approach that we developed for this study could be applied more broadly to unresolved questions about human brain evolution," says Fisher.
This research was supported by the Max Planck Society, Donders Centre for Cognitive Neuroimaging, Radboud University Medical Centre, BBMRI-NL, Hersenstichting-Nederland, NWO, European Union FP7, NIH, BMBF Germany, Federal State, Ministry of Cultural Affairs & Social Ministry of Mecklenburg-West Pomerania, Siemens Healthineers, InterSystems (Caché-Campus), German Research Foundation, Nomis Foundation.

Current Biology, Gunz et al.: "Neandertal introgression sheds light on modern human endocranial globularity"

Current Biology (@CurrentBiology), published by Cell Press, is a bimonthly journal that features papers across all areas of biology. Current Biology strives to foster communication across fields of biology, both by publishing important findings of general interest and through highly accessible front matter for non-specialists. Visit: To receive Cell Press media alerts, contact

Cell Press

Related Evolution Articles from Brightsurf:

Seeing evolution happening before your eyes
Researchers from the European Molecular Biology Laboratory in Heidelberg established an automated pipeline to create mutations in genomic enhancers that let them watch evolution unfold before their eyes.

A timeline on the evolution of reptiles
A statistical analysis of that vast database is helping scientists better understand the evolution of these cold-blooded vertebrates by contradicting a widely held theory that major transitions in evolution always happened in big, quick (geologically speaking) bursts, triggered by major environmental shifts.

Looking at evolution's genealogy from home
Evolution leaves its traces in particular in genomes. A team headed by Dr.

How boundaries become bridges in evolution
The mechanisms that make organisms locally fit and those responsible for change are distinct and occur sequentially in evolution.

Genome evolution goes digital
Dr. Alan Herbert from InsideOutBio describes ground-breaking research in a paper published online by Royal Society Open Science.

Paleontology: Experiments in evolution
A new find from Patagonia sheds light on the evolution of large predatory dinosaurs.

A window into evolution
The C4 cycle supercharges photosynthesis and evolved independently more than 62 times.

Is evolution predictable?
An international team of scientists working with Heliconius butterflies at the Smithsonian Tropical Research Institute (STRI) in Panama was faced with a mystery: how do pairs of unrelated butterflies from Peru to Costa Rica evolve nearly the same wing-color patterns over and over again?

Predicting evolution
A new method of 're-barcoding' DNA allows scientists to track rapid evolution in yeast.

Insect evolution: Insect evolution
Scientists at Ludwig-Maximilians-Universitaet (LMU) in Munich have shown that the incidence of midge and fly larvae in amber is far higher than previously thought.

Read More: Evolution News and Evolution Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to