We humans are proud of our large brains, which are responsible for our ability to plan ahead, communicate, and create. Inside our skulls, we pack, on average, 86 billion neurons – up to three times those of our primate cousins. For years, researchers have tried to discover how we can develop so many brain cells. Now, they’re getting one step closer: A new study shows that a single amino acid change in a metabolic gene helps our brains develop more neurons than other mammals — and even more so than our extinct cousins, the Neanderthals.
Brigitte Malgrange, a developmental neurobiologist at the University of Liège, who was not involved in the study, says the discovery is “really a breakthrough.” One amino acid change is Really, really important And it leads to incredible consequences for the brain.”
What makes our brain human has been the interest of neurobiologist Wayland Hautner at the Max Planck Institute for Molecular Cell Biology and Genetics for years. In 2016, his team found that there is a mutation in ARHGAP11B The gene, which is present in humans, Neanderthals and Denisovans but not in other primates, caused the production of more cells that develop into neurons. Although our brains are roughly the same size as Neanderthals, the shapes of our brains differ and we have devised complex techniques that no one else has ever developed. Therefore, Huttner and his team set out to find genetic differences between Neanderthals and modern humans, particularly in cells that give rise to neurons in the neocortex. This area behind the forehead is the most recently developed part of our brain, where the main cognitive processes occur.
The team focused on TKTL1, a gene with a single amino acid change in modern humans – from lysine to arginine – from the version found in Neanderthals and other mammals. By analyzing previously published data, the researchers found that TKTL1 It is mainly expressed in progenitor cells called radial basal glia, which give rise to most cortical neurons during development.
The researchers introduced both human and ancient versions of the gene to mice, which usually express neither form during development. The brains of the mice with the human version produced more radial basal glia cells, which in turn developed into more cortical neurons, than the mice with the older version.
The team also wondered whether TKTL1 It affected the deep folding of the human brain, an architecture that allows us to compress additional neurons inside our skulls. Mice completely lack these folds, but they are rodents, despite carrying the old version of TKTL1It has some folds. When researchers introduced the human version of the gene to rodents, the animals produced more cortical neurons and had larger brain folds, researchers report today in Sciences. “I wasn’t expecting to see an increase in [folds]says first author Anneline Pinson, a Max Planck postdoctoral researcher. “It makes sense because we have more neurons, but looking at them was so amazing and amazing.”
Next, the researchers used CRISPR technology to eliminate the problem TKTL1 in the cells of the neocortex of the fetus; Tissues lacking the gene produce fewer radial basal glia cells. Finally, the team compared the effect of both copies of the gene on brain organelles made up of human embryonic cells floating in Petri dishes. The human version again resulted in more progenitor cells and eventually more neurons than the old gene. Although additional genes may be involved, the discovery “demonstrates that this gene is an essential player,” in shaping our large brains, Huttner says.
The team also investigated how to do this TKTL1 It exerts its effect experimentally in human tissues and mice. TKTL1 It encodes an enzyme that helps cells produce fatty acids that are important in cell division. The researchers suspect that the extra fatty acids produced by the human version allow the progenitor cells to grow and divide more, resulting in more neurons.
With its multiple experiments, Alison Mootri, a neuroscientist at the University of California, San Diego School of Medicine, says that “it’s a solid game.” However, he wished the team had also explored changes in electrical activity in the altered brain organelles. He and his team last year showed it new 1another gene with a copy unique to modern humans that altered appearance, growth, and electrical activity of these organelles. if it was TKTL1 The results hold, he says, “We are building a list of genes likely to influence neural development and have been positively selected among humans.”
For Christoph Zollikofer, a paleoanthropologist at the University of Zurich, the new paper offers a “completely new gun…smoke” that shows how our brains differed from those of Neanderthals. But he cautions that the data cannot resolve the debate about Neanderthal mental abilities. Brain size and neuron numbers do not always translate into higher intelligence; For him, better cognition is all about the connections between neurons.
Benson and Hotner understand this point. However, Huttner says, “Having more neurons probably isn’t a bad thing.”