The complexity of human language sets us apart significantly from our primate cousins. A single gene may have played a key role in this difference, concludes new research published in the journal Nature Communications.
Mice speak differently from human variant
“ This discovery surprised us a lot.", recalls researcher Yoko Tajima, lead author of the publication. By replacing the mouse NOVA1 gene with its human version, scientists expected to cause severe motor dysfunction. Produced in neurons, the NOVA1 protein had in fact been discovered in patients with opsoclonus-myoclonus syndrome, a neurological disorder characterized by brief, involuntary eye and muscle movements. But mice with the human variant of NOVA1 showed no motor problems. On the other hand, they squeaked differently! " The calls of newborn mice to their mothers and of adult male mice to female mice had changed in pitch and complexity", explains Yoko Tajima.
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At first glance, the human version of NOVA1 doesn't seem much different from the many other animals, both mammals and birds, that also possess it. However, a single amino acid, isoleucine, is substituted by a valine near the middle of its sequence, at position 197. This small modification, unique to humans, is enough to alter the molecules to which the NOVA1 protein is supposed to bind. These molecules are RNAs, the derivatives of DNA that serve as intermediaries for protein production.
NOVA1 binds to molecules involved in vocalization
“ NOVA1 binds directly to RNAs in the brain to regulate their activity", up or down," the researchers explain. Using a new method specifically developed to identify RNAs linked to NOVA1, the scientists observed that human NOVA1 always bound in the same way as mouse NOVA1 to RNAs linked to motor functions, but not to those linked to language! We were completely surprised to find that the human version affected binding sites in midbrain neurons (central region of the brain, editor's note) which code for vocalization" explains Robert Darnell, who led this work.
These neurons in the midbrain are notably involved in breathing, coordination, timing, and amplitude of vocalization. But NOVA1 is also present in the mouse cortex, a more recent brain region that influences voice pitch and frequency modulation and duration, which could be another way the protein influences spoken language. "The mechanisms by which NOVA1 influences vocalization, whether from a motor or neuronal point of view, are a very important point that we want to address next," comments Yoko Tajima.
The closest ancient human lineages did not possess NOVA1
Suspecting a key role for NOVA1 in the emergence of complex human language, scientists are looking for its human version in the genomes of ancient related lineages. In the eight Neanderthal genomes and the one Denisovan genome examined, all possessed the NOVA1 of non-human animals. The emergence of our version of NOVA1 therefore occurred after the split between Homo sapiens and these now-extinct human lineages, approximately 200,000 years ago.
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“ Our data show that an ancestral population of modern humans in Africa evolved the human variant, which then became dominant, perhaps because it conferred advantages related to vocal communication." suggests Robert Darnell. Much later, around 50,000 years ago, this population then left Africa and spread around the world, taking the precious gene with it.
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