What makes your brain different from that of a Neanderthal?

What makes your brain different from that of a Neanderthal?

Scientists have discovered a glitch in our DNA that may have helped distinguish the minds of our ancestors from those of Neanderthals and other extinct relatives.

The mutation, which has occurred over the past hundreds of thousands of years, is spurring the development of more neurons in the part of the brain we use for our most complex forms of thought, according to a new study published Thursday in Science.

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“What we found is a gene that definitely helps make us human,” said Wieland Huttner, a neuroscientist at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, and one of the authors of the study.

The human brain allows us to do things that other living species cannot, such as using full language and making complicated plans for the future. For decades, scientists have compared the anatomy of our brains with those of other mammals to understand how these sophisticated abilities evolved.

The most obvious feature of the human brain is its size – four times larger than that of chimpanzees, our closest living relatives.

Our brain also has distinctive anatomical features. The region of the cortex just behind our eyes, known as the frontal lobe, is essential for some of our most complex thoughts. According to a 2018 study, the human frontal lobe has many more neurons than the same region in chimpanzees.

But comparing humans with living apes has a serious flaw: our most recent common ancestor with chimpanzees lived about 7 million years ago. To fill in what has happened since then, scientists have had to resort to the fossils of our most recent ancestors, known as hominins.

By inspecting the skulls of hominids, paleoanthropologists have discovered that the brains of our ancestors increased significantly in size around 2 million years ago. They grew to the size of living humans around 600,000 years ago. Neanderthals, among our closest extinct hominid relatives, had brains as big as ours.

But Neanderthal brains were elongated, whereas humans are more spherical in shape. Scientists cannot say what explains these differences. One possibility is that various brain regions of our ancestors changed in size.

In recent years, neuroscientists have begun to study ancient brains with a new source of information: pieces of DNA preserved inside hominin fossils. Geneticists have reconstructed entire genomes of Neanderthals as well as their eastern cousins, the Denisovans.

Scientists focused on potentially crucial differences between our genome and the genomes of Neanderthals and Denisovans. Human DNA contains approximately 19,000 genes. The proteins encoded by these genes are mostly identical to those of Neanderthals and Denisovans. But the researchers found 96 human-specific mutations that changed the structure of a protein.

In 2017, Anneline Pinson, a researcher in Huttner’s lab, was reviewing this list of mutations and noticed one that altered a gene called TKTL1. Scientists know that TKTL1 becomes active in the developing human cortex, particularly in the frontal lobe.

“We know the frontal lobe is important for cognitive function,” Pinson said. “So that was a good hint that this might be an interesting candidate.”

Pinson and his colleagues did initial experiments with TKTL1 in mice and ferrets. After injecting the human version of the gene into the animals’ developing brains, they found that it caused mice and ferrets to produce more neurons.

Next, the researchers conducted experiments on human cells, using fragments of fetal brain tissue obtained through the consent of women who had abortions at a hospital in Dresden. Pinson used molecular scissors to extract the TKTL1 gene from cells in the tissue samples. Without it, human brain tissue produced fewer so-called progenitor cells that give rise to neurons.

For their latest experiment, the researchers set out to create a miniature Neanderthal-like brain. They started with a human embryonic stem cell, modifying its TKTL1 gene so that it no longer carried the human mutation. Rather, it carried the mutation found in our relatives, including Neanderthals, chimpanzees, and other mammals.

They then placed the stem cell in a bath of chemicals that caused it to grow into a clump of developing brain tissue called a brain organoid. He generated brain progenitor cells, which then produced a miniature cortex made up of layers of neurons.

The Neanderthal-like brain organoid produced fewer neurons than organoids with the human version of TKTL1. This suggests that when the TKTL1 gene mutated, our ancestors could produce extra neurons in the frontal lobe. Although this change did not increase the overall size of our brain, it could have rearranged its wiring.

“It’s really a tour de force,” said Laurent Nguyen, a neuroscientist at the University of Liege in Belgium who was not involved in the study.

The new finding doesn’t mean that TKTL1, on its own, holds the secret to what makes us human. Other researchers are also looking at the list of 96 protein-altering mutations and conducting their own organoid experiments.

Other members of Huttner’s lab reported in July that two other mutations alter the rate at which developing brain cells divide. Last year, a team of researchers from the University of California, San Diego discovered that another mutation appears to alter the number of connections human neurons make to each other.

Other mutations may also be important for our brains. For example, as the cortex grows, individual neurons must migrate in order to find their place. Nguyen observed that some of the 96 mutations unique to humans altered genes that are likely involved in cell migration. He speculates that our mutations may make our neurons move differently than the neurons in a Neanderthal’s brain.

“I don’t think that’s the end of the story,” he said. “I think more work is needed to understand what makes us human in terms of brain development.”

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