How single mutation may have led humans to become more intelligent than Neanderthals

The variation of a single protein in the brain of modern humans may be responsible for their superior cognitive abilities compared to Neanderthals, a new study suggests.

Researchers assessed the effect of a change in a single amino acid building block which is linked to greater nerve cell production in the brain’s frontal lobe.

“Modern humans differ from apes and Neanderthals by this single amino acid change,” scientists, including those from the Max Planck Institute of Molecular Cell Biology and Genetics in Germany, say in the study published on Thursday in the journal Science.

The protein, known as transketolase-like 1 (TKTL1), is involved in the production of the brain’s basal radial glia, the workhorses that generate the frontal lobe during brain development – a part of the brain crucial for many cognitive abilities.

While Neanderthals and modern humans have brains of similar size, researchers say “very little” is known about whether the brains of the two species may have differed in terms of their neuron production during development.

In particular, they say both modern humans and Neanderthals feature a brain with a similar size neocortex – a brain region known to play a significant role in sensory perception, emotion, and cognition. Whether this indicates a similar number of nerve cells in the neocortex has remained unclear.

While previous studies have discovered a small number of proteins that differ between modern humans and our extinct relatives – the Neanderthals and Denisovans – scientists say the significance of these differences for the development of the modern human brain is also unknown.

In the research, scientists analysed one of these proteins – TKTL1 – that presents a single amino acid change in essentially all modern humans compared to Neanderthals.

This protein is found in progenitor cells of the foetus from which all neurons for the more advanced cortex brain regions derive. Notably, the level of TKTL1 is highest in the progenitor cells of the developing brain’s frontal lobe.

In modern humans, TKTL1 contains the amino acid arginine at a sequence position, whereas in Neanderthal TKTL1 it is the related amino acid lysine in this position.

When scientists introduced either the modern human or the Neanderthal variant of TKTL1 into the neocortex of mouse embryos, they found that a type of progenitor cells thought to be the driving force for a bigger brain increased with the modern human variant of TKTL1.

This effect was not observed with the Neanderthal variant of the protein.

As a consequence, researchers say, the brains of mouse embryos with the modern human TKTL1 contained more neurons.

Scientists conducted another experiment using lab-grown mini-human and Neanderthal brains, where they replaced the arginine amino acid in modern human TKTL1 with the lysine characteristic of Neanderthal TKTL1.

“We found that with the Neanderthal-type of amino acid in TKTL1, fewer basal radial glial cells were produced than with the modern human-type and, as a consequence, also fewer neurons,” study co-author Anneline Pinson said.

“This shows us that even though we do not know how many neurons the Neandertal brain had, we can assume that modern humans have more neurons in the frontal lobe of the brain, where TKTL1 activity is highest than Neanderthals,” Dr Pinson said.

Researchers suspect that the modern human TKTL1 increases the synthesis of certain membrane molecules needed to increase neuron production in the frontal lobe.

“This study implies that the production of neurons in the neocortex during fetal development is greater in modern humans than it was in Neanderthals, in particular in the frontal lobe. It is tempting to speculate that this promoted modern human cognitive abilities associated with the frontal lobe,” said Wieland Huttner, another author of the study.