A Mutation That Speaks: The NOVA1 Gene and the Evolution of Human Language

Can a single mutation change the course of a species? In the case of NOVA1 , a gene that regulates the way messenger RNAs are processed in our brains, the answer appears to be yes. Scientists are slowly unraveling the weight that a tiny difference, a single mutation in a sequence of DNA letters, had in the evolution of our species, distinguishing it from its extinct cousins, Neanderthals and Denisovans. That mutation may have helped shape some of our most distinctive abilities, like language.

The starting point of this story dates back to 2021, when a group of researchers, led by Alysson Muotri of the University of California, decided to look into the past through cerebral organoids , that is, “mini-brains” grown in the laboratory from stem cells . Their goal was to understand how the Neanderthal brain could have been different from ours, under the influence of a different NOVA1 gene. To do so, they used the CRISPR-Cas9 gene editing technique to replace the modern version of the NOVA1 gene with the archaic one, typical of Neanderthals and Denisovans, in human induced pluripotent stem cells. From these cells, they then grew cerebral organoids, three-dimensional structures in vitro that mimic the development of the human brain in its early stages. It was the first time that anyone had tried to revive, in the laboratory, a genetic trait belonging to our ancient relatives to observe how it would have influenced the growth of brain tissue.

The results were surprising. Organoids carrying the archaic variant of NOVA1 showed clear differences from those carrying the modern version. They grew more slowly and irregularly, with a more complex and pleated surface. Cells organized themselves differently, and neurons formed less efficient networks. Even electrical activity appeared altered. The picture that emerged was of a brain that followed a divergent developmental path from that of our species, suggesting that the modern version of NOVA1 had played a key role in refining the neuronal connectivity and cognitive abilities typical of Homo sapiens.

But the story doesn't end there. A few days ago, a new study added a fundamental piece . This time, researchers moved from miniature laboratory brains to living organisms. Using mice as a model, they introduced the human variant of NOVA1 into their genome to see if it could influence specific behaviors and skills. And once again, the results opened up unexpected scenarios. Mice with the sapiens version of the gene emitted different vocalizations than normal mice. Not only the number, but also the type and structure of the sounds were altered, so that the vocal communication of the mutant animals was much more complex and articulated than that of their normal relatives. In other words, the same mutation that in our ancestors heavily influenced the way the brain connects and communicates now seems to directly influence the modalities of vocal expression in another mammal.

The link with human language becomes inevitable. Even if the mouse does not speak, its vocalization is still a complex expression of brain activity and motor control. The fact that a single genetic variant is able to modify it suggests that the transition from Neanderthal to sapiens was not just a question of brain volume, but involved subtle changes, capable of improving neuronal plasticity and coordination between the brain and the vocal apparatus. This is where the NOVA1 mutation fits in, as a possible key cog in the emergence of that very human trait that is articulated language.

This is not the first time that a language-related genetic variant appears to be unique to modern humans. A case in point is that of the FOXP2 gene, often referred to as “the language gene.” Mutations in FOXP2 have been associated with specific speech and language disorders in humans, affecting the development of neural circuits crucial for verbal communication. Studies in animal models have shown that alterations in this gene can impair vocalizations and the learning of sounds, suggesting a fundamental role for FOXP2 in the evolution of human language abilities.

All this suggests that the evolution of our species has been, for a significant part, a process that has coupled the emergence of genetic variants capable of finely modifying the structure and functionality of the brain with the development of superior linguistic abilities. The few differences between archaic species and ours for the NOVA1 and FOXP2 genes are therefore not just any mutations, but represent the literal “genetic spark” that triggered a transition towards different minds and more complex languages ​​– with all that this entails in the social and cultural sphere.

An abrupt transition, at least for the capabilities accessible to our brains, dependent on a single step: the history of the evolutionary process and its possibilities appear increasingly surprising, at the crossroads between paleontology, archaeogenetics and evolutionism.

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