Neanderthal mutation alters brain development –

How our brain differs from the brain of Neanderthals? To answer this question, the researchers devised a new model system: They inserted a human Neanderthal gene into human stem cells and used it to grow tiny brains, known as brain organelles, in the laboratory. Organisms infected with the Neanderthal mutation evolved more slowly, shaped differently, and responded to stimuli differently from those containing only the genetic material of modern humans. Therefore, small genetic changes could have driven the evolution of our species’ brain.

Many studies dealing with the history of human evolution are based on archaeological discoveries and fossils. Such studies could hardly make any statements about brain development, because only the shape of the skull remains – the brains themselves do not ossify. For several years now, a technique has been created in medical research in which precise models of the brain are cloned from human stem cells. These so-called brain organoids are being used, for example, to research neurodegenerative diseases that are difficult to reproduce in animal models.

The Neanderthal gene in modern stem cells

A team led by Clipper Trujillo of the University of California is now using this organic approach to gain new insights into the brain evolution of our extinct ancestors. To do this, researchers first cataloged the genetic differences between modern humans and their closest relatives, Neanderthals and Denisovans. In doing so, they identified 61 similar genes in Homo sapiens, Neanderthals, and Denisovans, but showed certain deviations due to mutations.

One of these genes, NOVA1, is known for its role in brain development. It affects many other genetic products that are involved in the formation and networking of nerve cells. One mutation distinguishes a modern human genetic variant from that found in Neanderthals and Denisovans. The researchers wrote: “We hypothesize that this genetic change was an important event in the evolution of the modern human brain.” To see the effect of this mutation, they introduced the Neanderthal variant of NOVA1 into human stem cells with the help of the Crispr / Cas9 gene scissors. From these genetically modified stem cells, they grew brain organoids that mimicked the characteristics of a Neanderthal brain.

One mutation, many effects

Even with the naked eye, the organisms in the Neanderthal brain looked different from those that contained only the genetic material of modern humans: they were smaller and had a more complex surface. Closer analyzes revealed more differences: old brain organelles developed more slowly and synapses – the connections between neurons – were less effective. When researchers stimulated brain tissue with electrical signals, Neanderthal organelles showed stronger reactions in the early stages, but unlike modern brain organelles, they did not synchronize to form networks.

“It’s great to see that changing a single base pair in human DNA can change the way the brain is wired,” says Alison Motory, Trujillo’s colleague. “We don’t know exactly how and when this change occurred in our evolutionary history. But it does seem important and can help explain some of our recent skills in social behavior, language, adaptation, creativity, and use of technology.”

In the future, researchers want to use brain organelles to gain more knowledge about the development of our brain. This study focused on just one gene that differs between modern humans and our extinct relatives. Next, we want to look at the other 60 genes and see what happens if any one or a group of two or more genes are altered, ”Motrie says. The combination of stem cell biology, neuroscience and ancient genetics makes it possible to develop and test hypotheses. Completely new about brain function in early humans.

Quelle: Cleber Trujillo (University of California San Diego) et al., Science, Doi: 10.1126 / science.aax2537

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