One Gene Results in Major Differences Between Neanderthals & Modern Humans Brain Development

The first convincing proof that modern people had cognitive superiority over Neanderthals

About 400,000 years ago, the ancestors of modern humans and Neanderthals diverged into different lineages, with our ancestors staying in Africa and those who became Neanderthals migrating north into Europe. A large exodus of modern humans from Africa around 60,000 years ago brought the two species back into contact, and they interbred. Nowadays, contemporary humans with non-African ancestry have 1-4% Neanderthal DNA. But by 30,000 years ago, our distant relatives had been extinct as a separate species, leaving us to wonder how we managed to outcompete them.

It has long been believed that Neanderthals were our brutish, illiterate cousins. Some claim that our ancestors were more intelligent than Neanderthals, however this claim could not previously be verified empirically. But that notion has been challenged as the remnants of Neanderthal material culture showed they made art, music and understood symbolism.

As a result of the successful sequencing of Neanderthal DNA from a fossilized finger discovered in a Siberian cave, fresh knowledge about how Neanderthal biology differed from our own has emerged during the past ten years. For example, only 96 amino acids, the components of proteins, were found to be different between Neanderthals and contemporary humans when researchers sequenced the first complete Neanderthal genome in 2014. Now, ground-breaking research

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has uncovered substantial variations between the brain development of modern humans and Neanderthals, while not supporting the assumption.

The experiment entailed introducing a Neanderthal brain gene into ferrets, mice, and organoids, which are essentially lab-grown "mini-brains" made of human stem cells. The studies found that the Neanderthal version of the gene was connected to a slower generation of neurons in the cortex of the developing brain, which the researchers suggested may account for contemporary humans' greater cognitive ability.

TKTL1 and hominin cortical neurogenesis. The single lysine-to-arginine substitution in modern human TKTL1 leads to greater bRG numbers than in Neanderthals. These bRG in turn generate more neocortical neurons in modern humans. Because TKTL1 expression in fetal human neocortex is particularly high in the developing frontal lobe, these findings imply that the frontal lobe of modern humans contains more neurons than that of Neanderthals.

Specifically, the most recent research focuses on the TKTL1 gene, which is important in the development of new neurons in the brain. The gene's human and Neanderthal versions are separated by base resulting in a completely different amino acid. When the Neanderthal variety was implanted into mice, researchers discovered that fewer neurons were produced, especially in the frontal lobe, which houses the majority of cognitive activities. The number of brain progenitor cells in the mice with the human variant was substantially higher. The fetal tissue produced fewer progenitor cells and neurons than it typically would when the researchers synthesized neocortex cells from a human fetus to create the ancestral version. The same held true when they implanted the ancestor form of TKTL1 into brain organoids, tiny structures made from human stem cells that resemble the human brain.

The scientists hypothesized that this protein might be causing neural progenitor cells, which eventually give rise to neurons, to multiply as the brain grows, particularly in the neocortex, a region crucial in cognitive function.

Given that Neanderthal and human brains appear to have been around the same size in fossil records, modern humans' neocortices are either denser or occupy a bigger part of the brain. The scientists express their amazement that such a minor genetic variation may have such a profound impact on neocortex development. The number of neurons in the human brain is roughly double that of chimpanzees and bonobos. The humans who inherited this gene, however, experienced a huge rise in the number of brain cells as a result… perhaps providing them a cognitive advantage over their Neanderthal relatives. Although it does affect the brain's fundamental computing power, having more neurons does not necessarily make someone smarter.

1. Pinson, A., Xing, L., Namba, T., Kalebic, N., Peters, J., Oegema, C. E., Traikov, S., Reppe, K., Riesenberg, S., Maricic, T., Derihaci, R., Wimberger, P., Pääbo, S., & Huttner, W. B. (2022). Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals. Science (New York, N.Y.), 377(6611). https://doi.org/10.1126/science.abl6422