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Studying Neanderthal mini-brains, scientists unlock clues to evolution  – Boston, Massachusetts

Boston, Massachusetts 2021-02-11 14:00:07 –

HScientists have inserted genes from an extinct cousin into a human brain organoid (a real miniature version) in a laboratory dish with the aim of learning what makes our brain different from the Neanderthal brain. I saw it grow.

According to researchers at the University of California, San Diego, modern human DNA shares most of its genetic code with archaic species such as Neanderthals and Denisovans, but unshared genes are particularly important for evolution. It may have been important.

They used CRISPR genome editing technology to replace modern genes with archaic Neanderthal mutants within human cortical organoids, which are 3D structures grown from stem cells that mimic nerve development in the cerebral cortex.

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“My question was what makes us different from other species, including extinct relatives,” said Senior Researcher Allison Muotri. “This idea is the most novel aspect here.”

After comparing archaic DNA sequences to those of human populations around the world today, Muotri and his team used the protein-encoding gene NOVA1 in a study published Thursday. Science.. NOVA1 is found in both modern and archaic DNA, but of the more than 20,000 protein-coding genes, only 61 have unique mutations found in modern humans that are not shared with archaic relatives. It is one of the genes of.

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NOVA1 plays a management role as a master regulator of the developing nervous system and synaptogenesis. As a result, changes made by introducing Neanderthal variants into the minibrain affect many other genes and are easier to detect. Genetic pathways are associated with conditions such as autism and schizophrenia.

Muotri’s team noticed changes in neurodevelopment after inserting archaic genes in place of modern genes, but are careful not to consider them good or bad. In archaic NOVA1, nerve synapses fired at a faster rate. That is, neurons mature faster than modern human neurons.

Muotri speculated that there was a reason why modern humans evolved with genes that develop more slowly. He pointed out the difference between humans and chimpanzees as an example: baby chimpanzees grow much faster than humans. While human parents are still caring for their children, they can independently hunt and feed themselves early on. However, because of its slow development in the early stages, the human brain later becomes much more complex.

“Perhaps a good experiment would be to go to a chimpanzee and add a human version of that gene,” Muotri said. “Will it slow down brain development and make the chimpanzee more cognitively human?”

Such experiments are not performed in Muotri. He then hopes to use the same genome editing method to test the effects of archaic variants of the remaining 60 modern-specific protein-coding genes. The results form a catalog of genetically modified organisms to build a better understanding of the evolutionary journey of the human brain.

Muotri’s ambitions move faster than technical limits. Even before technologies such as CRISPR and organoids became available, he wanted to do such research using Neanderthal genes. However, you can also qualify your research by using relatively new technologies. He knows that CRISPR is not perfect and can unintentionally hit different regions of the genome. Organoids mimic the development of the brain, but they are not the same as the actual brain of the actual body and cannot be associated with specific behaviors. Still, he believes the study may have biomedical implications in the future.

“It’s a very useful model for advancing science and better understanding how the brain develops and how our genetic background affects it,” said the National Institute of Mental Health. Said Michael Gregory, who studies the genetics of Neanderthals in Japan. Not involved in this study.

According to Muotri, most scientific research on archaic DNA focuses on what is in common with the past, rather than the genetic code that separates us from the past. The genetic code shared with Neanderthals has been shown to offer advantages such as adaptation to high altitudes and drawbacks such as susceptibility to diabetes.

“The opportunity to use a similar technique with changes in other genes opens up a world of scientific possibilities,” Gregory said.

This study was conducted on two cell lines from humans with different neurotypical developments, and experts were able to understand how ancient genetic variants affect different populations, with different ancestry, race, and And hope that more can be done with multiple cell lines from the background of neurodiversity.

“Thinking about what makes us human is an important question for everyone, whether you’re a scientist or not,” Gregory said. “And it’s really important to understand how evolution has influenced and shaped us, and who we are today and what.”



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