Scientists have uncovered a flaw in our DNA that may have contributed to our ancestors’ brains differing from those of Neanderthals and other extinct cousins.
According to a new research published in Science on Thursday, the mutation, which occurred in the last few hundred thousand years, stimulates the production of additional neurons in the area of the brain that humans use for our most sophisticated types of reasoning.
“What we discovered is one gene that undoubtedly helps to making us human,” said Wieland Huttner, a neurologist from Dresden’s Max Planck Institute of Molecular Cell Biology and Genetics and one of the study’s authors.
The human brain enables humans to accomplish things that other living creatures cannot, such as use full-fledged language and make complex future plans. Scientists have been comparing the anatomy of our brain to that of other mammals for decades in order to understand how those sophisticated faculties evolved.
The most noticeable trait of the human brain is its size: it is four times larger than that of chimps, our nearest living cousins.
Our brain has different anatomical characteristics as well. The frontal lobe, located immediately beyond our eyes in the cortex, is critical for some of our most sophisticated thinking. According to a 2018 research, the human frontal lobe contains much more neurons than the equivalent area in chimps.
However, comparing humans to current apes has a fundamental flaw: our most recent common ancestor with chimps lived about seven million years ago. To fill in the gaps, scientists have had to rely on remains of our more recent relatives, known as hominins.
Paleoanthropologists studying hominid skeletons discovered that our predecessors’ brains grew considerably in size beginning about two million years ago. By 600,000 years ago, they had grown to the size of contemporary people. Our nearest extinct hominid ancestors, the Neanderthals, had brains as large as ours.
However, Neanderthal brains were elongated, while our brains are more spherical. Scientists are unable to explain the discrepancies. One idea is that different parts of our ancestors’ brains grew in size.
In recent years, neuroscientists have started to investigate ancient brains using a new source of data: DNA fragments trapped within hominid fossils. Geneticists have recreated the full genomes of Neanderthals and their Denisovan relatives.
Scientists have identified potentially significant discrepancies between our genome and that of Neanderthals and Denisovans. Human DNA comprises around 19,000 genes. These genes encode proteins that are almost similar to those found in Neanderthals and Denisovans. However, researchers discovered 96 human-specific mutations that altered the structure of a protein.
Dr. Huttner’s lab researcher Anneline Pinson was going through that list of mutations in 2017 when she found one that changed a gene called TKTL1. TKTL1 is known to become active in the growing human brain, particularly in the frontal lobe.
Dr. Pinson said, “We know that the frontal lobe is critical for cognitive activities.” “So it was a good clue that it may be an attractive candidate.”
Dr. Pinson and her colleagues first tested TKTL1 in mice and ferrets. They discovered that putting the human form of the gene into the developing brains of the animals allowed both mice and ferrets to generate more neurons.
Following that, the researchers conducted studies on human cells, utilising baby brain tissue acquired with the agreement of women who had abortions at a Dresden hospital. Dr. Pinson extracted the TKTL1 gene from the cells in the tissue samples using molecular scissors. Human brain tissue developed fewer so-called progenitor cells, which give birth to neurons, without it.
The researchers set out to build a miniaturised Neanderthal brain for their last experiment. They began with a human embryonic stem cell and edited its TKTL1 gene to remove the human mutation. Instead, it contained the mutation prevalent in our cousins, such as Neanderthals, chimps, and other animals.
They next immersed the stem cell in a chemical bath, which stimulated it to form a clump of growing brain tissue known as a brain organoid. It produced progenitor brain cells, which then gave rise to a miniature cortex composed of layers of neurons.
The organoids with the human form of TKTL1 produced fewer neurons than the organoids with the Neanderthal-like brain organoid. This implies that when the TKTL1 gene was altered, our forefathers might have produced additional neurons in the frontal lobe. While this modification did not expand our brain’s total size, it may have restructured its circuitry.
“This is really a tour de force,” said Laurent Nguyen, a neurologist from Belgium’s University of Liège who was not involved in the research. “It’s amazing that such a minor adjustment has such a huge influence on neuron development.”
The new discovery does not imply that TKTL1 alone holds the key to understanding what makes us human. Other researchers are also looking at the list of 96 protein-changing mutations and are performing organoid tests of their own.
Dr. Huttner’s team members announced in July that two additional mutations alter the rate at which growing brain cells divide. Another mutation seems to modify the amount of connections human neurons make with each other, according to a team of researchers at the University of California San Diego last year.
Other mutations may potentially be beneficial to our brains. Individual neurons, for example, must migrate as the cortex grows in order to reach their right position. Dr. Nguyen discovered that several of the 96 human-specific mutations affected genes involved in cell migration. He speculates that our mutations may cause our neurons to move differently from neurons in the brain of a Neanderthal.