What makes your brain different from a Neanderthal?

Scientists have discovered a defect in our DNA that may have helped separate our ancestors’ minds from those of Neanderthals and other extinct relatives.

The mutation, which originated in the past hundreds of thousands of years, stimulates the development of more neurons in the part of the brain we use for our most complex forms of thinking, according to a new study published in Science Thursday.

“What we found is one gene that definitely contributes to making us human,” said Welland Huttner, a neuroscientist at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, and one of the study’s authors.

The human brain allows us to do things that other living things cannot do, such as using perfect language and making complex plans for the future. For decades, scientists have been comparing the anatomy of our brain with that of other mammals to understand how those sophisticated faculties evolved.

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

Our brain also has distinct anatomical features. The area of ​​the cortex behind our eyes, known as the frontal lobe, is essential to some of our most complex thoughts. According to a study from 2018, the human frontal lobe contains a much higher number of neurons than the same area in chimpanzees.

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

After examining the skulls of hominins, paleoanthropologists found that the brains of our ancestors had increased dramatically in size about two million years ago. They reached the size of living humans about 600,000 years ago. Neanderthals, among our closest extinct hominin relatives, had brains as large as ours.

But the brains of Neanderthals were elongated, while humans have a more spherical shape. Scientists cannot determine the cause of these differences. One possibility is that different regions of our ancestors’ brains changed in size.

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

Scientists have focused on potentially crucial differences between our genomes and the genomes of Neanderthals and Denisovans. Human DNA contains about 19,000 genes. The proteins encoded by those genes mostly match those found in Neanderthals and Denisovans. But the researchers discovered 96 human-specific mutations that altered the protein’s structure.

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

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

Benson and colleagues conducted preliminary experiments with TKTL1 in mice and rodents. After injecting the human version of the gene into the brains of developing animals, they found that it caused mice and rodents to make more neurons.

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

In their final experiment, the researchers set out to create a miniature brain similar to that of a Neanderthal. They started with a human embryonic stem cell, and modified the TKTL1 gene so that it would not have the human mutation. Instead, it carried the mutation found in our relatives, including Neanderthals, chimpanzees, and other mammals.

Then they placed the stem cell in a bath of chemicals that prompted it to turn into a mass of developing brain tissue, called a brain organoid. It generated original brain cells, which then produced a miniature cerebral cortex made up of layers of neurons.

The Neanderthal-like brain organoid made fewer neurons than the organoid with the human version of TKTL1. This indicates that when the TKTL1 gene is mutated, our ancestors can produce additional neurons in the frontal lobe. While this change did not increase the overall size of our brain, it may have reorganized its wiring.

“This is really a strength journey,” said Laurent Nguyen, a neuroscientist at the University of Liège in Belgium, who was not involved in the study.

The new discovery does not mean that TKTL1, on its own, provides the secret of what makes us human. Other researchers are also looking at the list of 96 protein-modifying mutations and running experiments of their own.

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

Other mutations may also be important to our brains. For example, as the cortex develops, individual neurons need to migrate to find their proper niche. Nguyen noted that some of the 96 mutations unique to humans are altered genes that are likely to be involved in cell migration. He speculates that our mutations might make our neurons move differently from the neurons in the Neanderthal brain.

“I don’t think it’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.”

This article originally appeared in the New York Times.