Human brain genes trigger monkeys to grow larger brains

the evolutionary expansion of the human brain, especially the new cerebral cortical layer, is associated with cognitive abilities such as reasoning and language. There is a gene called ARRHGAP11B, expressed only in humans, that triggers brain stem cells to form more stem cells, a larger prerequisite for the brain. Past studies have shown that when ARRHGAP11B is expressed at non-physiologically high levels in mice and ferrets, it leads to the expansion of the neo-cerebral cortical layer, but its correlation with primate evolution is unclear.Researchers at the Max Planck Institute's Institute of Molecular Cell Biology and Genetics (MPI-CBG), in collaboration with colleagues from the Kawasaki Central Research Institute of Experimental Animals (CIEA) and Keiji University in Japan, found that when this gene is expressed in macaques to the physiological level of the human body, it causes the cerebral cortical layer to swell. This suggests that the AHGAP11B gene may have led to the expansion of the cerebral cortical layer during human evolution. The researchers published their findings in the journal Science, entitled "Human-specific ARHGAP11B increases size and folding of the primate neocortex in the fetal marmoset"."The new human cerebral cortical layer is the youngest cerebral cortical layer in evolution and is three times largeer than the brain cortical layer of a close relative of a human chimpanzee. During evolution, the folds of the new cerebral cortical layer increased to accommodate limited skull space. A key question for scientists is how the new human cerebral cortical layer has become so huge. In a 2015 study, Wieland Huttner, found that under the influence of the human-specific gene ARHGAP11B, mouse embryos produced more neurogenetic cells and could even fold the normally unfolded new cortical layer. The results show that the ARHGAP11B gene plays a key role in the evolutionary expansion of the new human cortical layer.The rise of human-specific genesAbout 5 million years ago, the human-specific gene ATHGAP11B was a partial copy of the common gene ARHGAP11A, evolving along the evolutionary linelogy that led to Neanderthals, Denisovans, and now humans, forming chimpanzees after separating from chimpanzees. In a follow-up study in 2016, Wieland Huttner's team found surprising reasons why the ARRHGAP11B protein contains 47 human-specific amino acid sequences that are not found in the AHGAP11A protein and are critical to ARRHGAP11B's ability to increase brain stem cells.Specifically, a C-to-G base replacement found in the ARRGAP11B gene resulted in the loss of 55 nucleotides in the ARRHGAP11B Messenger RNA, resulting in a change in the reading box, resulting in a human-specific, functionally critical sequence of 47 amino acids. This base replacement may have occurred much later than the gene appeared (about 5 million years ago), about 1.5 million to 500,000 years ago. This point mutation is not uncommon, but in the case of ARRHGAP11B, the advantage of forming a larger brain seems to have immediately affected human evolution.The effects of genes on monkeys, however, it is unclear whether the human-specific gene ATHGAP11B may also cause new brain cortical growth in non-human primates. To study the problem, Wieland Huttner teamed up with Erika Sasaki of the Central Research Institute of Kawasaki, Japan, and Hideyuki Okano of Keshiko University, which pioneered a technique that could produce genetically modified non-human primates. The study's lead author, postdoctoral student Michael Heide, traveled to Japan to work directly with colleagues on site.They produced genetically modified common velvet monkeys, a New World monkey, that develop a new brain cortical layer that expresses the human-specific gene ATHGAP11B, but they usually do not have it. Like Germany, Japan has the same high ethical standards and regulations for animal research and animal welfare. In Japan, the brains of 101-day-old common velvet monkey fetuses (50 days before normal birth) were obtained and sent to MPO-CBG for detailed analysis.Michael Heide explains: "We did find that the cerebral cortical layer of a normal velvet monkey is enlarged and the surface of the brain is folded. Its corted plate is also thicker than normal. In addition, we can see an increase in the number of glial progeniton cells in the lower substrate of the heart, as well as an increase in the number of upper neurons, a type of neuron that increased during the evolution of primates. "Researchers now have functional evidence that ARHGAP11B led to the expansion of the primate's new cerebral cortical layer., who led the study, added: "Our analysis is limited to velvet monkey fetuses because we expect this expression of human-specific genes to affect the development of the new cerebral cortical layer of velvet monkeys. Given the unforeseen consequences of brain function after the birth of a fetus, we consider this to be a prerequisite -- ethically mandatory -- to first determine the effect of ATHGAP11B on the development of the new cerebral cortical layer of fetal velvet monkeys. Thethat the results suggest that the human-specific AHGAP11B gene may have led to the expansion of the new cerebral cortical layer during human evolution. (Bio Valley Bioon .com)