A single gene could pave the way for increased human intelligence by dramatically increasing the number of brain cells in key areas of the brain.
The gene appears to be unique to humans: It is found in modern humans, Neanderthals and another extinct human lineage, the Denisovans, but not in chimpanzees.
This small piece of DNA may have laid the basis for a huge expansion of the human brain by allowing a region of the brain called the neocortex to accommodate many more neurons.
“It’s incredible that just one small gene can influence the phenotype of the stem cells that contributed most to the expansion of the neocortex,” said Marta Florio, a doctoral student in molecular cell biology and genetics at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, and lead author of the study.
Still, this gene is likely just one of many genetic variations that make human cognition special, Florio said.
Expanding Brain
The evolution from primitive apes to humans with complex language and culture took millions of years.
About 3.8 million years ago, Australopithecus afarensis, a species represented by the iconic “Lucy” fossil of an early human ancestor, had a brain volume of just under 30 cubic inches (500 cubic centimeters), about one-third the size of a modern human brain.
By about 1.8 million years ago, Homo erectus had a brain roughly twice the size of Australopithecus.
Homo erectus also showed evidence of tool use, fire use, and more complex social groups.
By the time anatomically modern humans, and their lost relatives, the Neanderthals and Denisovans, emerged, brain volume had expanded to about 85 cubic inches (1.4 liters).
Most of this growth occurred in a region of the brain called the neocortex.
“The neocortex is really interesting because it’s home to the cognitive abilities that, in some ways, make us human, like language and reasoning,” Florio told Live Science.
The neocortex is so big because it is packed with neurons, or brain cells, but what genetic changes caused this explosion of neurons?
Single gene
To answer this question, Florio and his thesis supervisor, Dr Wieland Huttner, a neurobiologist also at the Max Planck Institute, studied a type of neural progenitor cell – a stem cell that divides during embryonic development to form brain cells.
In mice, these cells divide once to form neurons, but in humans, the same cell types divide many times to form vast numbers of neurons.
Florio isolated these cells and analyzed the genes that were active in both mice and humans at the peak of brain development. (The researchers looked at this process in both 13-week-old human fetuses, whose tissue was provided by women after abortions, and in mice at 14 days pregnant.)
The researchers found that a particular gene, called ARHGAP11B, was turned on and highly active in human neural precursor cells but was completely absent in the mouse cells.
This tiny piece of DNA is just 804 letters, or bases, long and was once part of a much longer gene, but for some reason this piece was duplicated and the duplicated piece was inserted into the human genome.
The team then inserted this DNA fragment into the brains of mice, where it was expressed (turned on).
Mice normally have a small, smooth neocortex, but the mice with the gene grew something that resembled a larger neocortex. These enhanced brain regions contained large amounts of neurons, and some began to form the characteristic folds, or convolutions, seen in the human brain, which pack dense brain tissue into a small space. (The researchers did not confirm whether the mice actually got smarter, but that’s a possible avenue for future research, Florio said.)
Unique Genes
Building on previous work by Evan Eichler and his colleagues at the University of Washington, the team also looked at the genomes of several other species and found that Neanderthals and Denisovans have the gene, but chimpanzees and mice do not.
This suggests that the gene emerged shortly after humans diverged from chimpanzees, paving the way for the rapid expansion of the human brain.
Still, this genetic change is unlikely to fully explain human smarts, Huttner said. Although both humans and Neanderthals had large brains, Huttner said, unique human intelligence may have more to do with how brain cells form and neural networks organize over time.
This gene produces far more functioning neurons, but “how those neurons are wired so that humans can fly to the moon and Neanderthals can’t” is likely a function of genes expressed in neurons, rather than genes expressed in precursor cells, Huttner told Live Science.
The gene was published today (February 26th) in the journal Science.