In a lab at Rockefeller University in New York, a mouse squeaks. But this is no ordinary squeak. It is a strange, complex sound, unlike anything heard from a mouse before. The difference lies in a single gene — a gene that may hold the key to one of humanity’s most defining traits: the ability to speak.

Language is a hallmark of our species. But how did this remarkable ability emerge? Words and sentences leave no fossils, and the origins of speech remain shrouded in mystery. A new study offers a tantalizing clue. Researchers have identified a genetic variant unique to humans that may have played a pivotal role in the evolution of language — with some help from some humble rodents.

The gene, known as NOVA1, is no stranger to scientists. It has been studied for decades due to its important role in brain development. But what makes the human version of NOVA1 special is a single amino acid change. A tiny tweak in the genetic code sets us apart from our ancient cousins, the Neanderthals and Denisovans. When scientists inserted this human variant into mice, the animals began to vocalize differently, producing more complex sounds.

“For me, that was like, ‘Bingo!’” Dr. Robert Darnell, a neuroscientist at Rockefeller University and one of the study’s authors, told The NY Times.

A Singular Change, A Singular Species

This protein is highly conserved across species, meaning it has remained largely unchanged throughout evolution. But in modern humans, there is a single amino acid difference — a switch from isoleucine to valine at position 197. As such, the human variant of NOVA1, known as I197V, is found exclusively in Homo sapiens. It emerged sometime between 250,000 and 500,000 years ago, after our ancestors split from Neanderthals and Denisovans. This timing suggests that the change may have provided an evolutionary advantage, helping early humans communicate in ways that their cousins could not.

“The fact that we have this singular variant unique to the earliest humans, and can link this to vocalization, suggests it might be connected to the evolution of complex language,” Dr. Darnell said.

To test this idea, Dr. Darnell and his team used CRISPR gene-editing technology to replace the mouse version of NOVA1 with the human variant. These “humanized” mice, known as Nova1hu/hu, were then compared to their wild-type counterparts in a series of experiments. The results were striking. Baby mice with the human gene squeaked differently when calling for their mothers. Adult males, courting females, produced more intricate vocalizations.

“The human-variant mice produced different sequences than the wild-type mice did,” said Dr. Erich Jarvis, a neuroscientist at Rockefeller University and co-author of the study.

The greatest differences were seen in high-frequency calls, some of which are too high-pitched for humans to hear. . These changes suggest that the human-specific NOVA1 mutation may influence the development of vocal communication in subtle but meaningful ways.

NOVA1 is known to regulate alternative splicing, a process that allows a single gene to produce multiple proteins. In the Nova1hu/hu mice, this process was altered in specific ways, particularly in genes involved in brain function and vocalization. 

Not the Only Gene, But It Could Be a Key Piece of the Puzzle

NOVA1 is not the first gene linked to language. In 2001, researchers identified FOXP2, often called the “language gene.” But while FOXP2 is involved in human speech, it is not unique to us — Neanderthals and even some animals share similar variants. NOVA1, on the other hand, is found only in humans.

“The exciting thing about NOVA1 is that there is now another kid on the block,” said Dr. Wolfgang Enard, a geneticist at Ludwig Maximilian University of Munich who was not involved in the study.

NOVA1 is just one piece of a much larger puzzle. Language likely arose from mutations in hundreds of genes, as well as anatomical changes in the throat and brain. It’s most likely that Neanderthals and Denisovans could speak as well. “I wouldn’t say it’s ‘the’ language gene,” Dr. Jarvis cautioned. “But where does NOVA1 fit into that whole combination? It’s one of the last steps.”

From Language Genes to Medicine

Beyond shedding light on our evolutionary past, the discovery of NOVA1’s role in vocalization could have practical applications. Understanding how the gene works may help scientists develop new treatments for speech disorders, from developmental delays in children to language impairments caused by strokes or neurodegenerative diseases.

“That’s certainly a possibility,” said Liza Finestack, a speech-language pathologist at the University of Minnesota who was not involved in the study. “The genetic findings might someday allow scientists to detect, very early in life, who might need speech and language interventions.”

For now, the researchers are focused on unraveling the intricate pathways that connect genes like NOVA1 to the brain’s ability to produce and understand language. They also hope to engineer mice with multiple human language-related genes, including NOVA1 and FOXP2, to see if the animals can produce even more complex vocalizations.

“Our study shows that at least one genetic change uniquely found in humans can impact vocal communication in a non-human species,” Dr. Jarvis said. “But spoken language likely came about through a combination of genetic changes.”

In the end, the story of NOVA1 is not just about how humans learned to speak. It’s about what makes us uniquely human — and how a single genetic tweak may have helped us find our voice.

The findings appeared in the journal Nature Communications.