Scientist Have Found a Key Gene That Makes Our Brain Larger Than Other Apes
For the first time, scientists have been able to explain why humans have a more evolved brain than other species.
At the DNA level, humans share 99 percent and 98 percent sequence similarity with Chimpanzees and Gorillas, respectively. But surprisingly our brain is about three times bigger than that of these apes. In fact, of all primates, we possess the largest brain. Scientists have long wondered why humans have such developed brains compared to other species. Since ancient times, many experts have attempted to address this question from different perspectives.
However, a group of scientists at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK, recently discovered a more obvious answer to this mystery. They compared the growth of the human brain to that of chimps and gorillas and identified a key gene responsible for the human brain’s greater development.
Dr. Madeline Lancaster and her team at the MRC Laboratory of Molecular Biology studied the brains of humans, chimpanzees, and gorillas to understand what provokes the human brain to develop more neurons. However, instead of using real brain tissue, the researchers used brain organoids in their experiment. An organoid isn’t a true organ; it is indeed a mini and simplified 3D tissue that’s grown in the lab to mimic the actual organ. Their findings from the study have been published recently in the Cell journal.
Our body has a special type of cells — known as stem cells — that can produce different types of other cells. Neural progenitors are such kinds of stem cells that make neurons in the brain at the early stage of development. In the beginning, these progenitor cells have a cylindrical structure, which allows them to be readily divided into more new cells.
These cylindrical progenitor cells eventually mature, elongate, and transform into actual neurons. Thus the more progenitor cells multiply, the more neurons are formed. The use of brain organoids has helped researchers to understand this transformation process in chimpanzees, gorillas, and humans.
According to a previous report, this maturation and change of cell form occur in mice within an hour. That’s why mice brains have 1000 times fewer neurons than humans. On the other hand, this transition event takes a much longer time in humans and apes. Neuronal progenitor cells in gorillas and chimps require about five days to develop into mature neuron cells.
Human progenitor cells take even more times — around seven days — to slow down their multiplication and transform into fully developed neurons. As a result, progenitor cells in the human brain get more time to multiply and generate more neurons. Perhaps this is one of the prime reasons why humans have three times more neurons than their closest relatives in the animal kingdom.
According to Dr. Lancaster, this delay in the transition of cell shape at the initial phase of brain formation allows us to grow more neurons and thereby evolve into a more intelligent life form.
In an interview with ScienceDaily, she states, “It’s remarkable that a relatively simple evolutionary change in cell shape could have major consequences in brain evolution. I feel like we’ve really learned something fundamental about the questions I’ve been interested in for as long as I can remember — what makes us human.”
After identifying the cause of larger brain development, Dr. Lancaster and her team conducted an RNA sequence analysis to better understand the molecular mechanisms acting behind this preferential development. They sequenced mRNA derived from human, chimp, and gorilla brain organoids to find out which genes were expressed or silenced throughout the course of brain formation.
By comparing the gene expression data from humans, chimpanzees, and gorillas' brain organoids, scientists marked a gene called ‘ZEB2’ which has a profound impact on this process of development.
They noticed that in gorilla brain organoids ZEB2 gene gets activated much sooner than that in the human brain organoids. Researchers believe this earlier activation of the ZEB2 gene is responsible for the maturation of progenitor cells. This means that the later this gene is turned on, the more time progenitor cells will have to generate neurons.
To further validate their finding, scientists adopted gene-level editing by the CRISPR mechanism. They delayed the effect of the ZEB2 gene in gorilla brain organoids, which enabled these organoids to grow more like a human brain and produced much more neurons.
Conversely, turning on the ZEB2 gene earlier in human brain organoids slowed down the multiplication of neuronal cells and resulted in much fewer neuron cells as like the brain of apes. Thus it is evident that activation of the ZEB2 gene has a fundamental regulatory role during the early stage of brain development, as well as determining the extent of brain growth.
Since the research was conducted on organoid models — which do not fully reflect the function of an actual brain — more details need to be researched by using the animal model. But there is no doubt that this experiment has provided us with some vital insights into evolution and brain formation. These tiny tissue models on glass plates made it possible to perform such incredible studies.
