A tiny genetic change that emerged in early humans may have played a role in our unique vocal communication abilities, according to a new study published in Nature Communications.
Researchers at The Rockefeller University have identified a single amino acid substitution in a protein called NOVA1 that’s unique to modern humans and appears to influence vocalization patterns in mice engineered to carry this human-specific genetic variant.
The study provides insight into how small genetic changes accumulated during human evolution might have contributed to our distinctive capacity for spoken language.
“NOVA1 is a neuronal RNA-binding protein expressed in the central nervous system and is essential for survival in mice and normal development in humans,” explained the research team, led by Yoko Tajima, César D. M. Vargas, and Robert B. Darnell.
NOVA1 is highly conserved across mammals, meaning it’s remained virtually unchanged through millions of years of evolution. But somewhere in our lineage after the split from our common ancestors with Neanderthals and Denisovans, a single letter in our genetic code changed, resulting in the substitution of an isoleucine with a valine at position 197 of the NOVA1 protein.
This I197V variant is now nearly universal in modern humans. When the researchers analyzed genomic data from over 650,000 people, they found that only six individuals carried the ancestral version of this gene – five of whom were of Asian descent.
To understand what functional effects this tiny genetic change might have, the team used CRISPR gene editing to create “humanized” mice carrying the modern human version of NOVA1 rather than the ancestral version present in most mammals.
Remarkably, these mice developed normally, but when researchers analyzed their brains, they found subtle differences in how NOVA1 affected the processing of RNA – the intermediate molecule between DNA and protein – in genes related to brain function.
The most intriguing finding came when they recorded vocalizations from these mice. Both pups separated from their mothers and male adults during courtship exhibited altered ultrasonic vocalization patterns compared to normal mice.
“These findings suggest that this human-specific NOVA1 substitution may have been part of an ancient evolutionary selective sweep in a common ancestral population of Homo sapiens, possibly contributing to the development of spoken language through differential RNA regulation during brain development,” the researchers noted.
Dr. Erich D. Jarvis, a co-author on the paper and a specialist in the neurogenetics of vocal learning, has previously proposed that certain core brain circuits for vocal communication are conserved across vertebrates, from fish to humans. The discovery that NOVA1 is highly expressed in brain regions linked to vocalization in mice supports the idea that modifying these ancient circuits could have contributed to humans’ advanced vocal abilities.
The study builds on previous research into genes potentially involved in human language evolution. FOXP2, sometimes called “the language gene,” has been studied extensively since its discovery in a family with severe speech and language problems. Interestingly, the researchers note that the vocalization changes in their humanized NOVA1 mice share similarities with those previously observed in mice carrying human versions of FOXP2.
However, unlike FOXP2 variants which are also present in Neanderthals, the NOVA1 I197V change appears unique to modern humans, suggesting it arose more recently in our evolutionary history.
The researchers conducted extensive molecular analyses to understand how this single amino acid change affects NOVA1’s function. They found that while the change doesn’t affect the protein’s ability to bind to RNA, it does alter which specific RNAs are processed differently, particularly those involved in vocalization.
Professor Simon Fisher, director of the Max Planck Institute for Psycholinguistics, who was not involved in the study, commented that the research “adds an important piece to the puzzle of how genetic changes specific to modern humans might have influenced our capacity for complex communication.”
While the study doesn’t claim that this single genetic change gave humans the gift of language, it suggests that accumulation of such changes in genes affecting brain development and vocal circuits could have collectively contributed to our species’ unique communication abilities.
The findings also highlight how studying the effects of human-specific genetic changes in animal models can provide insights into human evolution that cannot be obtained from fossil records alone.
As we continue to compare modern human genomes with those of our extinct relatives, and test the functions of human-specific genetic variants, we may gain deeper understanding of the biological underpinnings of the traits that make us uniquely human.
The research was published in Nature Communications on February 8, 2025.