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Humans with Neanderthal DNA Hold Clues to Modern Brain Evolution

Humans who carry particular Neanderthal DNA fragments have heads that are slightly less rounded, revealing genetic clues to evolution of modern brain shape and function, a study has found.

"We captured subtle variations in endocranial shape that likely reflect changes in the volume and connectivity of certain brain areas," said Philipp Gunz from the Max Planck Institute for Evolutionary Anthropology in Germany.

"Our aim was to identify potential candidate genes and biological pathways that are related to brain globularity," said Amanda Tilot from Max Planck Institute for Psycholinguistics.

The researchers took advantage of the fact that living humans with European ancestry carry rare fragments of Neanderthal DNA buried in their genomes, as a result of interbreeding between Neanderthals and the ancestors of modern Europeans.

Different people carry different fragments, which are scattered through the genome, according to the study published in the journal Current Biology.

Researchers analysed cranial shape and identified stretches of Neanderthal DNA in a large sample of modern humans, relying on magnetic resonance imaging (MRI) brain scans and genetic information for about 4,500 people.

Based on computed tomographic scans, they computed the endocranial shape differences between Neanderthal fossils and modern human skulls.

The researchers used this contrast to assess endocranial shape in thousands of MRI brain scans of living people.

They used information from sequenced genomes of ancient Neanderthal DNA to identify Neanderthal 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," said Simon Fisher, a geneticist at the Max Planck Institute for Psycholinguistics.

"Here we found that, in carriers of the relevant Neanderthal fragment, UBR4 is slightly down-regulated in the putamen.

"For carriers of the Neanderthal PHLPP1 fragment, gene expression is slightly higher in the cerebellum, which would be predicted to have a dampening effect on cerebellar myelination," Fisher said.

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," said Gunz.

"The basal ganglia also contribute to diverse cognitive functions, in memory, attention, planning, skill learning, and potentially speech and language evolution," he said.
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