How does our brain differ from that of Neanderthals? To answer this question, researchers have created a new model system: They introduced a Neanderthal gene into human stem cells and used them in the laboratory to grow mini-brains, known as brain organoids. The organoids with the Neanderthal mutation developed more slowly, were shaped differently and reacted differently to stimuli than those that only contained the genetic material of modern humans. Small genetic changes could therefore have advanced the brain development of our species.
Many studies that deal with the history of human evolution rely on archaeological finds and fossils. However, such studies can hardly make any statements about the development of the brain, because only the shape of the skull remains – the brains themselves do not petrify. For some years now, a technology has been established in medical research in which tiny models of the brain are reproduced from human stem cells. These so-called brain organoids are used, for example, to research neurological diseases that are difficult to reproduce in animal models.
Neanderthal gene in modern stem cells
A team led by Cleber Trujillo from the University of California has now used this organoid approach to gain new insights into the brain development of our extinct ancestors. To do this, the researchers first cataloged genetic differences between modern humans and their two closest relatives, the Neanderthals and the Denisovans. In doing so, they identified 61 genes that are similar in Homo sapiens, Neanderthals and Denisova, but show specific deviations due to mutations.
One of these genes, NOVA1, is known for its role in brain development. It influences numerous other gene products that are involved in the formation and networking of nerve cells. A single mutation distinguishes the gene variant of modern humans from that found in Neanderthals and Denisovans. “We assume that this genetic change was an important event in the evolution of the modern human brain,” the researchers write. To find out what influence the mutation had, 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 properties of the Neanderthal brain.
One mutation, many effects
Even with the naked eye, the Neanderthal brain organoids looked different than those that only contained the genetic material of modern humans: They were smaller and had a more complex surface. Closer analyzes revealed further differences: the archaic brain organoids developed more slowly and their synapses – the connections between nerve cells – were less functional. When the researchers stimulated the brain tissue with electrical signals, the Neanderthal organoids showed stronger reactions in the early stages, but in contrast to modern brain organoids, they did not synchronize to form networks.
“It is fascinating to see that a single base pair change in human DNA can change how the brain is wired,” says Trujillo’s colleague Alysson Muotri. “We don’t know exactly how and when this change took place in our evolutionary history. But it seems significant and could help explain some of our modern skills in terms of social behavior, language, adaptation, creativity and use of technology. “
In the future, the researchers want to use brain organoids to gain further knowledge about the evolution 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 find out what happens if any one or a combination of two or more genes is changed, ”says Muotri. The combination of stem cell biology, neuroscience and paleogenetics makes it possible to create and test completely new hypotheses about the brain function of early humans.
Source: Cleber Trujillo (University of California San Diego) et al., Science, doi: 10.1126 / science.aax2537