How a gene mutation produces higher intelligence

Summary: Rare genetic mutations that lead to blindness also appear to be associated with higher than average intelligence, according to a new study.

A source: University of Leipzig

Synapses are the communication points in the brain through which nerve cells “talk” to each other. Disruption of this connection leads to diseases of the nervous system, because altered synaptic proteins, for example, can disrupt this complex molecular mechanism. These are mild symptoms, but can also lead to very severe disabilities in affected people.

Professor Tobias Langenhan and Professor Manfred Heckman, two neurobiologists from Leipzig and Würzburg, became interested when they read in a scientific publication about a mutation that damaged a synaptic protein.

At first, the patients attracted the attention of scientists because mutations caused them to go blind. However, doctors then found that the patients were also moderately intelligent.

Langenhan, a professor at the Rudolf Schönheimer Institute of Biochemistry at the Faculty of Medicine, said: “It is very rare for a mutation to improve rather than lose function.

Two neurobiologists from Leipzig and Würzburg have been using fruit flies for many years to analyze synaptic functions.

“Our research project is designed to incorporate mutations in patients into the fly’s appropriate gene and use techniques such as electrophysiology to test what happens to synapses. We thought the mutation would make patients so smart because it would improve the communication between the neurons that contain the damaged protein, ”explains Langenhan.

“Of course, you can’t make these measurements on the synapses of the human brain. You have to use animal models. ”

“Fruit flies also contain 75 percent of the genes that cause disease in humans”

First, researchers, in collaboration with Oxford researchers, showed that a fly protein called RIM is molecularly similar to humans. This fly was essential for studying changes in the human brain. In the next step, neurobiologists introduced mutations into the fly’s genome that looked like those of a sick person. They then took electrophysiological measurements of synaptic activity.

“We have seen a significant increase in information at the synapses of mutated animals. This remarkable effect on the synapses of flies is likely to occur in the same or similar way in human patients and may explain the increase in their cognitive abilities, as well as their blindness, ”concluded Professor Langenhan.

Researchers have also discovered how the increase in synaptic transitions occurs when the molecular components in a conductive nerve cell that excite synaptic impulses come closer together as a result of mutations, leading to an increase in neurotransmitters. The new method was one of the methods used in the study of super-resolution microscopy.

Researchers have also discovered how the increase in synaptic transitions occurs when the molecular components in a conductive nerve cell that excite synaptic impulses come closer together as a result of mutations, leading to an increase in neurotransmitters. Image in public domain

“It gives us a tool that allows us to look at and even count individual molecules, and confirms that the molecules in the ignition cell are closer together than usual,” said Professor Langenhan, who assisted Professor Hartmut Schmidt’s research team. Karl Ludwig Institute in Leipzig.

“The project is a wonderful demonstration of how amazing animal models, such as fruit flies, can be used to better understand human brain disease. Animals are genetically very similar to humans. It is estimated that 75 percent of the genes that cause the disease in humans are also found in fruit flies, ”explains Professor Langenhan, citing further research at the Faculty of Medicine.

“We have launched several joint projects with the team of human geneticists, pathologists and the Center for Integrated Research and Treatment (IFB) AdiposityDiseases; Founded in a hospital at the University of Leipzig, they are studying the development of brain disorders, malignancies and obesity. Here, too, we introduce disease-causing mutations into fruit flies to replicate and better understand human disease. ”

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Author: Susan Huster
A source: University of Leipzig
The connection: Susan Huster – University of Leipzig
Photo: Image in public domain

Original study: Closed access.
Tobias Langenhan brain


CORD7, which enhances human cognition, increases the number of active mutation zones and synaptic output

See also

This is a diagram of the study

People with CORD7 (cone-rod dystrophy 7) mutations have increased oral IQ and working memory. This autosomal dominant syndrome is caused by the exchange of an amino acid R844H (human numbering) located in Section 3.10 With spiralstwoRIMS1 / RIM1 domain (Rab3-interacting molecule 1).

RIM is an evolutionarily preserved multi-domain protein and an important component of synaptic active zones, it is a centralized fast, Ca2+– release of neurotransmitters. The effect of CORD7 mutations on synaptic function remains unknown.

Here we are Drosophila melanogaster As a disease model to determine the effect of CORD7 mutation on RIM function and synaptic vesicle release.

For this purpose, using protein expression and X-ray crystallography, we decided on the molecular structure of the molecule. Drosophila ChtwoCompared to the domain with a resolution of 1.92 Å and its mammalian homologue, the location of the CORD7 mutation was found to be structurally preserved in RIM flies.

Further, CRISPR / Cas9 was used to generate genomic engineering kidney R915H CORD7 exchange encoding alleles or R915E, R916E exchange (fly numbering)10 spiral.

Through electrophysiological characterization using two electrode voltage clamps and focal recordings, we found that the CORD7 mutation had a non-dominant but partially dominant effect on synaptic conduction, resulting in faster synaptic, efficient release, and easier-to-remove basal volume. For a quick calcium chelator BAPTA.

an additional kidney The CORD7 allele increased the number of presynaptic active zones, but left their nanoscopic organization unhindered because Bruchpilot / ELKS / CAST detected super-resolution microscopy of the presynaptic storage protein.

We conclude that the CORD7 mutation leads to closer release connections, an immediate increase in the size of the release pool, and more release sites, thereby increasing the efficiency of synaptic conduction release.

These results suggest that strongly similar mechanisms may be based on the CORD7 disease phenotype in patients and may contribute to enhanced synaptic transmission and enhancement of their cognitive abilities.

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