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Summary: Researchers have identified a genetic region, HAR123, which can help explain what makes the human brain unique. Acting as a transcriptional potentator, HAR123 influences the development of neural progenitor cells, which give rise to neurons and glial cells, and plays a role in determining their relationship.
This regulation seems to support cognitive flexibility, a clearly human trait that implies the ability to adapt thought and replace obsolete knowledge. The discovery could advance in our understanding of brain evolution and genetic roots of neurological development disorders such as autism.
Key facts
Genetic switch: HAR123 controls the activity of the brain gene as a transcriptional enhancer. Cognitive impact: linked to advanced human features such as cognitive flexibility. Evolutionary difference: Human Human works differently from the Chimpanzee version.
Source: UCSD
The research of scientists of the Faculty of Medicine of San Diego of the University of California has thrown new light on an ancient question: what makes the human brain unique?
The discovery of the team comes from their research from human accelerated regions (Hars): Sections of the human genome that have accumulated an unusually high level of mutations as humans have evolved.
There is a lot of scientific interest in Hars, since they have the hypothesis of playing an essential role in the conference of specific human being, and also have links with neurological development disorders, such as autism.
A reason why scientists think that Hars confers specific features of humans is because they have undergone rapid changes in their genetic sequences since we separate ourselves from our nearest living relative, chimpanzee, approximately 5 million years ago.
Now, UC San Diego researchers have identified a particular HAR, called HAR123, which seems to be fundamental to shape the human brain.
The researchers found:
HAR123 In itself it is not a gene, but is a type of “molecular volume control known as transcriptional enhancer. Transcriptive potentiators control which genes are activated, how much they are activated, and at what times they are activated during the development of an organism. Through its role as a transcriptional enhancer, HAR123 promotes the development of neural progenitor cells, the cells that give rise to the two main types of neurons and glial cells.
Ultimately, HAR123 promotes a particularly advanced human trait called cognitive flexibility, or the ability to unlearn and replace previous knowledge.
In addition to providing new ideas about the biology of the human brain, the results also offer a molecular explanation for some of the radical changes that have occurred in the human brain in the course of our evolution.
This is compatible, for example, by the finding of the authors that the human version of HAR123 exerts different molecular and cellular effects that the Chimpanzee version in both stem cells and in precursor cells of neurons on a Petri plate.
More research is needed to more completely understand the molecular action of HAR123 and if the human version of HAR123 really confers specific neuronal features of humans. This line of research could lead us to a better understanding of molecular mechanisms that underlie many neurological development disorders, such as autism.
The study, published online in Science Advances, was directed by Miles Wilkinson, Ph.D., distinguished professor, and Kun Tan, Ph.D., assistant professor, both within the Department of Obstetrics, Gynecology and Reproductive Sciences at the UC School of Medicine of the UC San Diego. Wilkinson is also an affiliated faculty of the Institute of Genomic Medicine of the UC San Diego. The study was financed, in part, by subsidies of the National Institutes of Health and Genomics 10x. The authors do not declare competitive interests.
On this news of genetic research and neuroscience
Author: Miles Martin
Source: UCSD
Contact: Miles Martin – UCSD
Image: The image is accredited to Neuroscience News
Original research: open access.
“An ancient enhancer that quickly evolves in human lineage promotes neuronal development and cognitive flexibility” by Miles Wilkinson et al. Scientific advances
Abstract
An ancient enhancer that quickly evolves in human lineage promotes neuronal development and cognitive flexibility
The genetic changes that drive the evolution of humans from the human Chimpanzee division have been difficult to achieve. Here, we inform a promising candidate in a chromosomal region linked to neurological defects: 17p13.3.
We show that this 442-Nucleotide sequence, the human accelerated region (HAR) 123, is a preserved neuronal enhancer that promotes the formation of neural progenitor cells (NPC). While it is present in all mammals, HAR123 has evolved quickly since humans diverged from chimpanzees.
Human orthologists and chimpanzee HAR123 exhibit subtle differences in their neuronal development effects, and human Har123 uniquely regulates many genes involved in neural differentiation.
We identify direct objectives of the enhancer HAR123 and show that I do HAR123 downstream to promote the formation of human NPC. HAR123-KNockout mice exhibit a defect in cognitive flexibility and a change in the neural-gly relationship in specific hippocampus regions.
Our study has implications for neurological development disorders, which are often accompanied by an altered relationship of neural glia and have been related to Hars.
