Rosa Rubicondior: Refuting Creationism - A Simple Mutation Could Have Given Us the Power of Speech.

Model of the evolutionary timing for the 197th amino acid change in the NOVA1 gene, noting the Nova1^hu/hu mice generated in this study. Nova1^hu/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.

Tajima, Y., Vargas, C.D.M., Ito, K. et al (2024) (CC BY 4.0)

The Rockefeller University » A single protein may have helped shape the emergence of spoken language

In the simplistic creationist parody of evolution, intelligently designed to make cult members feel superior to real scientists, the evolution of something like speech in humans must have involved complex, specified, information, that humans alone have that other, lesser, species don't have. Of course, this could only be the result of intelligent design by a supreme intelligence who favours humans, its special creation, who can be whichever your favourite deity is, although it’s not religion because it doesn’t mention God or the Bible. Got it!

The surprising thing is that neither William A. Dembski, nor Michael J. Behe, leading Deception Institute fellows, have written a widely acclaimed (in creationist circles and in selected magazine and newspaper articles emanating from the Deception Institute, for its brilliant conclusive proof of the failure of 'Darwinism') book, detailing the sheer astounding complexity of the genetic basis for human speech, and how this proves we don't share a common ancestor with the African apes.

Perhaps they were aware already of the fact that the genetic basis for human speech involves, no such complexity, but just a single point mutation in a gene we share with the other apes and many other mammals.

Rather than proof of human exceptionalism, our ability to speak turns out to be evidence for common ancestry.

The mutation was discovered by researchers from The Rockefeller University and is a simple substitution of the amino acid isoleucine for valine, in the protein NOVA1 which resulted from the substitution of guanine (G) in the first position in the codon for isoleucine for adenine (A). So, the simplest of all mutations - a single point substitution of one nucleotide for another in a gene, may have enabled humans to speak.

What role does the protein NOVA1 play in human speech? NOVA1 (Neuro-oncological ventral antigen 1) is an RNA-binding protein that plays a significant role in alternative splicing regulation, particularly in the nervous system. It has been implicated in human brain development and cognitive functions, including those related to speech and language.

NOVA1 and Human Speech Evolution

A key study in 2021 by Trujillo et al. demonstrated that NOVA1 was subject to human-specific evolutionary changes. The research focused on a single nucleotide difference between modern humans and Neanderthals/Denisovans in the NOVA1 gene. When this archaic variant of NOVA1 was reintroduced into human brain organoids, it resulted in differences in neuronal connectivity, synaptic organization, and gene expression patterns. These differences suggest that the human-specific version of NOVA1 may have played a role in shaping modern human cognition and speech capabilities.

Potential Mechanisms in Speech

Neural Circuit Development: NOVA1 influences the splicing of mRNAs involved in synaptic plasticity and neuronal connectivity. Changes in these pathways could have contributed to the fine-tuning of circuits necessary for complex speech.
Motor Control of Speech: Given its role in cortical and motor system development, NOVA1 could be involved in the fine control of motor functions necessary for spoken language.
Cognitive and Memory Functions: Language involves working memory and complex cognitive processing, and NOVA1 is known to regulate genes implicated in these functions.
While NOVA1 is not the sole determinant of human speech, its evolution likely contributed to the neural adaptations that support our advanced linguistic capabilities.

Interestingly, the same mutation is not present in Neanderthals or Denisovans who had the same version of NOVA1 as other animals, so must have arisen in Homo sapiens after our evolutionary line diverged from theirs.

The researchers have published their findings, open access, in the journal Nature Communications, and explain it in a science news item from Rockefeller University:

A single protein may have helped shape the emergence of spoken language
The origins of human language remain mysterious. Are we the only animals truly capable of complex speech? Are Homo sapiens the only hominids who could give detailed directions to a far-off freshwater source or describe the nuanced purples and reds of a dramatic sunset?
Close relatives of ours such as the Neanderthals likely had anatomical features in the throat and ears that could have enabled the speaking and hearing of spoken language, and they share with us a variant of a gene linked to the ability to speak. And yet it is only in modern humans that we find expanded brain regions that are critical for language production and comprehension.

Now researchers from The Rockefeller University have unearthed intriguing genetic evidence: a protein variant found only in humans that may have helped shape the emergence of spoken language.

In a study published in Nature Communications, researchers in the lab of Rockefeller researcher Robert B. Darnell discovered that when they put this exclusively human variant of NOVA1—an RNA-binding protein in the brain known to be crucial to neural development—into mice, it altered their vocalizations as they called to each other.

The study also confirmed that the variant is not found in either Neanderthals or Denisovans, archaic humans that our ancestors interbred with, as is evidenced by their genetic traces that remain in many human genomes today.

This gene is part of a sweeping evolutionary change in early modern humans and hints at potential ancient origins of spoken language. NOVA1 may be a bona fide human ‘language gene,’ though certainly it’s only one of many human-specific genetic changes.

Robert B. Darnell, lead author
The Laboratory of Molecular Neuro-oncology
The Rockefeller University, New York, NY, USA.

Three decades in the making

Anatomical adaptations of the vocal tract and intricate neural networks enable our language capabilities. But the genetics behind them isn’t well understood.

One theorized genetic language driver is FOXP2, which codes for a transcription factor involved in early brain development. People with mutations in this gene exhibit severe speech defects, including the inability to coordinate lip and mouth movements with sound. Humans have two amino acid substitutions in FOXP2 that aren’t found in other primates or mammals—but Neanderthals had them too, suggesting that the variant arose in an ancestor of both human lineages. But some findings on FOXP2 have been disputed, and its role in human language development remains unclear.

Now NOVA1 has arisen as a candidate. The gene produces a neuron-specific RNA binding protein key to brain development and neuromuscular control that was first cloned and characterized by Darnell in 1993. It’s found in virtually identical form across a wide swath of the biosphere, from mammals to birds—but not in humans. Instead, we have our own unique form characterized by a single change of an amino acid, from isoleucine to valine, at position 197 (I197V) in the protein chain.

I197V isn’t the only amino acid substitution that distinguishes modern humans from other organisms, points out first author Yoko Tajima, a postdoctoral associate in Darnell’s lab. Several of them may be integral to brain development.

Such changes may have played important roles in the acquisition of characteristics that have contributed to the emergence, expansion, and survival of Homo sapiens.

DR. Yoko Tajima, first author.
The Laboratory of Molecular Neuro-oncology
The Rockefeller University, New York, NY, USA.

A specialist in how RNA binding proteins modulate gene expression, Darnell has been researching NOVA1 since the early 1990s, when he and his colleagues first identified it as the trigger of a neurologic autoimmune disorder called POMA that can cause extreme motor dysfunction. Recently they have begun to identify cases in which NOVA1 genetic variants are associated with developmental language and motor difficulties.

“Understanding NOVA1 has been a career-long effort for me,” he says.

The current study, led by Tajima, used CRISPR gene editing to replace the common NOVA1 protein found in mice with the human variant I197V. They then used advanced techniques such as cross-linking immunoprecipitation (CLIP) analysis, a method developed by Darnell, to identify the RNA binding sites of NOVA1 in the mouse midbrain.

The big reveal

The first notable discovery was that the human variant had no impact on RNA binding related to neural development or motor control. It operated exactly as the one it had replaced.

So what was it doing? The second significant finding gave them a hint: binding sites that were substantially affected by the human variant were located at genes that coded for RNAs related to vocalization.

Moreover, many of these vocalization-related genes were also found to be binding targets of NOVA1, further suggesting the involvement of NOVA1 in vocalization.

DR. Yoko Tajima.

We thought, wow. We did not expect that. It was one of those really surprising moments in science.

Robert B. Darnell.

Darnell’s lab then joined forces with Rockefeller’s Laboratory of Neurogenetics of Language, headed by Erich D. Jarvis, who studies the molecular and genetic mechanisms underlying vocal learning.

Altered communications

Over the next few years, the collaborators investigated the impact on vocalizations among mice of various ages in different contexts. They found altered vocal patterns among both pups of both sexes and adult males.

All baby mice make ultrasonic squeaks to their moms, and language researchers categorize the varying squeaks as four ‘letters’—S, D, U, and M. We found that when we ‘transliterated’ the squeaks made by mice with the human-specific I197V variant, they were different from those of the wild-type mice. Some of the ‘letters’ had changed.

Robert B. Darnell.

They found similar patterns when they studied the hopeful mating calls of male adult mice exposed to female adult mice in estrus.

They ‘talked’ differently to the female mice. One can imagine how such changes in vocalization could have a profound impact on evolution.

Robert B. Darnell.

The human element

The potential influence of I197V on human evolution became their next focus. To confirm that it wasn’t found in our nearest human relatives—the Neanderthals, who largely lived in Europe, and the Denisovans, named after the central Asian cave where they were discovered—the researchers compared eight human genomes with three high-coverage Neanderthal genomes and one high-coverage Denisovan genome.

As expected, our archaic relatives—from whom we are thought to have split about 250,000-300,000 years ago—had the same NOVA1 protein as all non-human animals.

They then combed through 650,058 modern human genomes in the dbSNP database, a catalog of short sequence variations drawn from people around the world. If an alternative to I197V existed, it would be found here.

Of those 650,058 people, all but six had the human variant. Those six had the archaic variant; because the samples are de-identified, details about them are unknown.

Our data show that an ancestral population of modern humans in Africa evolved the human variant I197V, which then became dominant, perhaps because it conferred advantages related to vocal communication. This population then left Africa and spread across the world.

Robert B. Darnell.

Disease and disorders

In the future, Darnell’s lab will investigate how NOVA1 regulates language function with an eye on language or developmental disorders.

We believe that understanding these issues will provide important insights into how the brain operates during vocal communications—and how its misregulation leads to certain disorders.

DR. Yoko Tajima.

Its neural pathways may come into play, for example, when various disorders renders someone unable to speak. Perhaps it influences the development of nonverbal autism; NOVA1 is one of the many genes linked to autism spectrum disorder. And in 2023, the lab reported on a patient with a NOVA1 haploinsufficiency whose neurological symptoms included a speech delay.

Our discovery could have clinical relevance in many ways, ranging from developmental disorders to neurodegenerative disease.

Robert B. Darnell.

Abstract

NOVA1, a neuronal RNA-binding protein expressed in the central nervous system, is essential for survival in mice and normal development in humans. A single amino acid change (I197V) in NOVA1’s second RNA binding domain is unique to modern humans. To study its physiological effects, we generated mice carrying the human-specific I197V variant (Nova1^hu/hu) and analyzed the molecular and behavioral consequences. While the I197V substitution had minimal impact on NOVA1’s RNA binding capacity, it led to specific effects on alternative splicing, and CLIP revealed multiple binding peaks in mouse brain transcripts involved in vocalization. These molecular findings were associated with behavioral differences in vocalization patterns in Nova1^hu/hu mice as pups and adults. Our 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.

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

Copyright: © 2024 The authors.
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

A single-point mutation in the NOVA1 gene exemplifies how minor genetic changes can lead to profound evolutionary shifts over time. NOVA1 is a crucial RNA-binding protein involved in alternative splicing, shaping how neurons develop and connect in the brain. In modern humans, a small difference in this gene, absent in Neanderthals and Denisovans, has been shown to alter neuronal connectivity and synaptic organization. These changes would have influenced cognitive abilities, including memory, learning, and motor control—key components necessary for the development of complex speech. Such a minute genetic tweak did not instantly grant Homo sapiens the ability to speak in full sentences, but over generations, it contributed to subtle refinements in brain circuitry that eventually supported the evolution of intricate language. It meant evolving humans were able to respond to evolutionary pressure because each refinement in these ability would have given us a significant advantage.

This stands in stark contrast to the creationist notion that human speech must have emerged fully formed by design or the complex ability must have been created by 'complex specified information' being inserted into the genome. Instead, it underscores the gradual, cumulative nature of evolution—where small, naturally occurring mutations provide incremental advantages that are honed by selection over time. NOVA1’s modification alone was not the cause of speech, but as part of a web of genetic and neural adaptations, it played a role in nudging human cognition toward the linguistic sophistication we now take for granted. The story of NOVA1 is a testament to the power of evolution’s tiny steps — showing that complexity arises not through sudden acts of creation but through the relentless refinement of biological systems over millennia.

Advertisement

Amazon