The human brain has something exceptional. Its relative size in relation to the rest of the body is the largest among all species. They just discovered the genetic key that endows mammals with big brains
A human brain weighs approximately 1,500 g. It is much smaller than that of the elephant, with 5 kg of brain, or that of the whale, with 7.8 kg. And, of course, there are many smaller ones. A macaw’s brain is the size of a shelled walnut, a monkey’s is the size of a lemon. A mouse’s brain measures just over a centimeter and weighs the same as a jellybean.
Now they’ve figured out what the size of a brain in different species depends on, why mammals have big brains and other species deal with tiny organs.
Reason is a “key” in the DNA of all species. That switch is a small RNA, called MIR3607, which is turned on during embryonic development in mammals with very large brains, such as humans, and remains turned off in those with small brains, such as mice.
When the switch is activated, the number of neural stem cells increases and thus the formation of neurons increases. These are the conclusions of a work by the Neurogenesis and cortical expansion led by Víctor Borrell, from the UMH-CSIC Neuroscience Institute in Alicante.
That this switch is activated, that MIR3607 is expressed during the development of the embryo, was selected by evolution to potentiate in most mammals the expansion of the cerebral cortex, the most evolved part of the brain.
The small size of the rodent brain
In rodents such as mice, the loss of this microRNA led to a small, smooth brain, unlike in most mammals, which evolved into large, folded brains.
The number of specific and unique genes in humans is relatively small, while the number of genes conserved and expressed in the cerebral cortex in different mammalian species during embryonic development is much higher. A fundamental question still to be resolved was how the expression of these highly conserved genes that guide the development of the cerebral cortex was regulated so differently during evolution in different species.
In an article published today by the magazine advances in science, researchers at the Institute of Neurosciences CSIC-UMH, in Alicante, led by Dr. Víctor Borrell, director of the group “Neurogenesis and cortical expansion”, investigated this question by focusing on a gene that gives rise to a microRNA called MIR3607. And they found that in species with small brains like the mouse, the loss of expression, or “silencing,” of MIR3607 during evolution led to a dramatic decrease in the size of the cerebral cortex, which ultimately determines size. of the brain. In addition, its cerebral cortex became smooth, compared to that of most mammals, which increased its surface through convolutions and grooves, in the form of a relief of peaks and valleys.
The genetic mechanisms underlying this secondary loss in rodent brain evolution were completely unknown until now. “With our work, we showed that the microRNA MIR3607 is expressed in embryo in the large cerebral cortex of primates and carnivores, such as the ferret, but not in the mouse.” highlights Victor Borrell.
MicroRNAs (miRNAs) are small RNAs that do not give rise to proteins, but rather regulate the expression of other genes, which is why they are essential during embryonic development. In fact, the evolution of different animal species follows the emergence of new miRNAs that promoted diversity during embryonic development. However, despite the ability of miRNAs to modulate gene expression, they have surprisingly received little attention in the context of brain evolution and expansion.
“With this work, we identified MIR3607 as an important regulator of the Wnt/β-Catenin signaling cascade, a pathway with fundamental functions in the embryonic development of the cerebral cortex, as it regulates processes such as stem cell proliferation and cell differentiation. . Our findings also fit with recent findings on the importance of miRNAs in early cortical development, regulating neural stem cell amplification and the homeostasis of the germ layer from which they arise,” explains Dr. Borrell.
setback in evolution
From an evolutionary point of view, these results suggest that “the loss of MIR3607 expression in the developing cerebral cortex may have been a key factor in the secondary reduction in brain size during rodent evolution. The absence of MIR3607 in the mouse embryonic cerebral cortex has raised the key and still unclear question of how its activation is regulated,” explains Kaviya Chinnappa, pre-doctoral researcher and first author of this work.
The general trend of mammalian evolution towards expansion and folding of the cerebral cortex was reversed in some groups of mammals, such as the New World monkeys and especially rodents, and their brains evolved to become smaller and smoother than those of mammals. your ancestors. “Our results identify for the first time that the loss of MIR3607 was selected during the evolution of small mammals, to decrease the size of the cerebral cortex in mice”, Borrell points out.
“MicroRNAs are generally highly conserved across animal species. The similarity of MIR3607 in humans, monkeys, ferrets and mice suggests conserved functionality for this microRNA in the mouse brain. Therefore, we reasoned that if we reexpress MIR3607 experimentally in the mouse embryonic brain , we could clarify its role during cortical development,” explains Chinnappa.