Researchers identify gene mutation to have the potential to induce higher intelligence in humans

When genes mutate, serious diseases of the human nervous system can result. Scientists from Leipzig University and the University of Würzburg have now used fruit flies to show how, in addition to the negative impact, mutation of a neuronal gene can have a beneficial impact—higher IQ in humans. They announced their discovery in the esteemed journal “Brain.”

Synapses are the points in the brain where nerve cells communicate with one another. Disruptions in this communication cause nervous system diseases because modified synaptic proteins, for instance, can affect this complex molecular mechanism. This can cause mild symptoms as well as severe disabilities in those who are affected.

Professors Tobias Langenhan and Manfred Heckmann of Leipzig and Würzburg, respectively, became interested in a mutation that injures a synaptic protein after reading about it in a scientific paper. The affected patients initially drew the attention of scientists because the mutation prompted them to go blind. However, doctors soon discovered that the patients had the above-average intellectual ability.

It’s very rare for a mutation to lead to improvement rather than loss of function.”

Tobias Langenhan, Professor, Faculty of Medicine, Rudolf Schönheimer Institute of Biochemistry

Langenhan was also the holder of a chair at RSIB.

For several years, two neurobiologists from Leipzig and Würzburg have studied synaptic functions in fruit flies.

“Our research project was designed to insert the patients’ mutation into the corresponding gene on the fly and use techniques such as electrophysiology to test what then happens to the synapses. It was our assumption that the mutation makes patients so clever because it improves communication between the neurons which involve the injured protein,” explains Langenhan. “Of course, you can’t conduct these measurements on the synapses in the brains of human patients. You have to use animal models for that,” he adds.

“75 percent of genes that cause diseases in humans also exist in fruit flies.”

First, the researchers demonstrated, in collaboration with Oxford scientists, that the fly protein RIM is molecularly similar to that of humans. This was necessary to investigate the changes in the human brain on the fly. The neuroscientists then inserted mutations into the fly genome that looks remarkably, like they did in sick people. They then measured synaptic activity electrophysiologically.

We actually observed that the animals with the mutation showed a much increased transmission of information at the synapses. This amazing effect on the fly synapses is probably found in the same or a similar way in human patients, and could explain their increased cognitive performance, but also their blindness.”

Tobias Langenhan, Professor, Faculty of Medicine, Rudolf Schönheimer Institute of Biochemistry

The researchers also discovered how enhanced transmission at synapses happens: the molecular components in the transmitting nerve cell that trigger synaptic impulses come close together as a consequence of the mutation effect, resulting in greater neurotransmission. One of the strategies used in the research was super-resolution microscopy, which was a new technique.

“This gives us a tool to look at and even count individual molecules and confirms that the molecules in the firing cell are closer together than they normally are,” comments Professor Langenhan who was assisted in the study by Professor Hartmut Schmidt’s research group from Leipzig’s Carl Ludwig Institute.

“The project beautifully demonstrates how an extraordinary model animal like the fruit fly can be used to gain a very deep understanding of human brain disease. The animals are genetically highly similar to humans. It is estimated that 75 percent of the genes involving disease in humans are also found in the fruit fly,” explains Professor Langenhan, directing to additional study on the subject at the Faculty of Medicine.

“We have started several joint projects with human geneticists, pathologists, and the team of the Integrated Research and Treatment Center (IFB) AdiposityDiseases; based at Leipzig University Hospital, they are studying developmental brain disorders, the development of malignant tumors, and obesity. Here, too, we will insert disease-causing mutations into the fruit fly to replicate and better understand human disease,” Langenhan concluded.