The mystery surrounding the origins of human language continues to intrigue the scientific community. The ability to communicate with a complex language distinguishes us from other animal species, and so far, there is no conclusive evidence that Neanderthals or other hominins could develop this skill with the same sophistication as Homo sapiens.

While there are indications that Neanderthals had the anatomical structures necessary to produce and perceive articulated sounds, the development of certain brain regions essential for language appears to have been exclusive to modern humans. Now, a recent study from Rockefeller University could shed new light on this question.

Researchers from Robert B. Darnell’s laboratory have identified a variant of the NOVA1 protein that may have played a key role in the emergence of spoken language. NOVA1 is an RNA-binding protein that plays a fundamental role in neural development. In a study published in Nature Communications, scientists demonstrated that introducing the human variant of NOVA1 into mice through CRISPR genetic editing significantly modified their vocalizations.

The most remarkable aspect of this discovery is that the variant in question is absent in Neanderthals and Denisovans, two archaic human species with whom our ancestors shared genes in the past. This suggests that the emergence of this mutation in our direct ancestors may have been linked to the development of language.

Studying the genetic basis of language is a complex endeavor. For decades, researchers have analyzed genes that might be involved in this ability, such as FOXP2, a transcription factor involved in early brain development. However, while it is known that mutations in FOXP2 cause severe speech impairments, its role in language evolution remains debated.

protein origin human language
Model of the evolutionary timing for the 197th amino acid change in the NOVA1 gene, noting the Nova1hu/hu mice generated in this study. Nova1hu/hu mice express the modern human-specific amino acid in the NOVA1 protein. The bottom panel shows the corresponding position within the KH2 domain of the NOVA1 protein. Amino acids structurally proximal (<5 Å) to the 197th amino acid, as predicted by AlphaFold2, are highlighted in pink. Credit: Y. Tajima et al.

NOVA1 has now emerged as a promising candidate. Identified in 1993 by Darnell himself, this protein is found in a wide variety of organisms, from mammals to birds, in nearly identical forms. However, in modern humans, it presents a distinctive mutation: a change from isoleucine to valine at position 197 of its protein chain (I197V). This small variation could have been crucial in developing our communication abilities.

To test the impact of the human variant of NOVA1, researchers replaced the mouse version of this protein with the human I197V form. They then analyzed the rodents’ vocalizations in different situations. They discovered that the pups emitted ultrasonic sounds with a different pattern than normal mice and that adult males altered their vocal repertoire when interacting with females during mating periods.

These findings were surprising to scientists since NOVA1 did not seem to alter motor functions or overall neural development but specifically affected the expression of genes related to vocalization. Yoko Tajima, the study’s lead author, points out that this result suggests NOVA1 may have played an important role in the evolution of human language.

To confirm the exclusivity of this mutation in modern humans, researchers compared genetic sequences from eight contemporary individuals with three high-quality Neanderthal genomes and one Denisovan genome. The results were clear: our archaic relatives retained the ancestral version of NOVA1, while all modern humans analyzed carried the I197V variant.

Additionally, 650,058 modern human genomes in the dbSNP database were analyzed, and only six individuals lacked the I197V variant, indicating that this mutation has become fixed in the human population with a frequency close to 100%. Researchers suggest that natural selection may have favored this variation due to its possible advantages in vocal communication, allowing it to spread worldwide following the migration of our ancestors from Africa.

Beyond its relevance to human evolution, this discovery could have clinical implications. NOVA1 is associated with neuromuscular development and has been linked to certain speech and developmental disorders. Darnell’s laboratory has identified variants of this gene in people with language delays and motor issues.

The team plans to investigate how NOVA1 regulation might be connected to autism spectrum disorders, particularly in cases where patients experience verbal communication difficulties. Additionally, they will study its potential role in neurodegenerative diseases that affect speech and communication abilities.

This study represents a significant step in understanding how our capacity for language may have evolved. While NOVA1 is not the only gene involved in this complex ability, its exclusive mutation in humans and its impact on mice vocalization suggest it may have been a key factor in the development of spoken language. In the future, further research could shed more light on its role in human evolution and its connection to language and communication disorders.

SOURCES

The Rockefeller University

Tajima, Y., Vargas, C.D.M., Ito, K. et al. A humanized NOVA1 splicing factor alters mouse vocal communications. Nat Commun 16, 1542 (2025). doi.org/10.1038/s41467-025-56579-2

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