Summary: New research suggests that a genetic variation in the NOVA1 proteins may have contributed significantly to the development of human discourse. Scientists tested this exclusive human version on mice and observed altered vocalizations, suggesting that vocal communication may have a part.
This variation wasn’t present in Neanderthals and Denisovans, which supported the study’s finding, which would indicate that it was present in both modern people. Researchers believe that this hereditary change may have affected the mind networks involved in sounds and contributed to the development of spoken language.
Further examination of 650, 058 human dna revealed that nearly all modern people carry this feature, pointing to its biological value. Future research will look into its possible correlations with language-related problems and developmental conditions.
Important Information:
- Human-Specific Variant: The NOVA1 proteins in modern humans carries a special biological alter not found in Neanderthals or Denisovans.
- Vocalization Impact: When introduced into animals, the human version altered their outspoken designs, hinting at a part in speech development.
- Biological Significance: Practically all modern people carry this version, suggesting it became prominent due to advantages in vocal conversation.
Origin: Rockefeller University
The causes of human speech remain strange. Are we the only creatures who are truly gifted with intricate language?
Are , Homo sapiens , the single hominids who could offer detailed directions to a far-off water source or explain the subtle purples and reds of a serious sunset?
Close relatives of own, such as the Neanderthals, probably had anatomical features in the mouth and ears that might have enabled the use of spoken language in conversation and hear, and they also share with us a version of a dna that is related to the ability to speak.
But just in contemporary people can we get expanded brain regions that are essential for vocabulary production and understanding.
Experts from The Rockefeller University have now discovered interesting genetic data: a protein version unique to humans that may have contributed to the development of spoken speech.
In a study published in , Nature Communications, researchers in the laboratory of Rockefeller researcher , Robert B. Darnell , discovered that when they put this entirely human version of NOVA1—an RNA-binding protein in the brain known to be essential to neurological development —into mice, it altered their noises as they called to each other.  ,
The study also demonstrated that the version, which is not present in either Neanderthals or Denisovans, archaic humans, as demonstrated by the genetic signs that are found in many human dna today.
” This protein is part of a sweeping biological change in early modern humans and suggestions at probable ancient origins of spoken vocabulary”, says Darnell, mind of the , Laboratory of Molecular Neuro-Oncology.
” NOVA1 , may be a bona fide human’ language gene,’ though certainly it’s only one of many human-specific genetic changes”.
Three decades in the making
Our language abilities are made possible by intricate neural networks and anatomical adaptations of the vocal tract. 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 who have mutations in this gene have a lot of severe speech problems, including the inability to synchronize lip and mouth movements with sound.
Neanderthals also had two amino acid substitutions in FOXP2, which are not found in other primates or mammals, giving the impression that the variant was a result of a cross between two 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“, she says.  ,
Since the early 1990s, Darnell, a specialist in how RNA binding proteins affect gene expression, has been studying NOVA1 since they first discovered it as the cause of a neurologic autoimmune disorder called POMA, which can lead to severe 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 finding was that motor control or neural development were not impacted by the human variant’s impact on RNA binding. It continued to function exactly as the one it had replaced.
So what was it doing? The second important finding provided a hint to them: binding sites that were in large part affected by the human variant were located at genes that encoded 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”, says Tajima.
” We thought,  , wow. We did not expect that”, Darnell says. One of those scientifically surprising moments occurred.
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
The collaborators studied the effects on vocalizations among mice of various ages and in various circumstances over the course of the next few years. They discovered altered vocal patterns in both adult males and pups of both sexes.
” All baby mice make ultrasonic squeaks to their moms, and language researchers categorize the varying squeaks as four’ letters ‘—S, D, U, and M”, Darnell notes.
” 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”.
When they examined the hopeful mating calls of male adult mice that were exposed to female adult mice in Estrus, they observed similar patterns. ” They’ talked’ differently to the female mice”, he says. One can only imagine how profoundly altered vocalizations could be.
The human element
Their next area of study was the potential impact of I197V on human evolution. 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.  ,
The dbSNP database, a catalog of short sequence variations drawn from people all over the world, then searched through 650, 058 modern human genomes. 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”, he suggests.
” This population then left Africa and spread all over the world.”
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 think that understanding these issues will reveal important insights into how the brain functions while speaking, and how its misregulation causes a number of disorders, Tajima writes.
Its neural pathways may come into play, for example, when various disorders renders someone unable to speak. One of the many genes linked to autism spectrum disorder is NOVA1, which may have an impact on the development of nonverbal autism.
And in 2023, the lab , reported , on a patient with a NOVA1 haploinsufficiency whose neurological symptoms included a speech delay.
According to Darnell,” Our discovery may have a wide-ranging clinical application, from developmental disorders to neurodegenerative disease.”
About this news from research in genetics and evolutionary neuroscience
Author: Katherine Fenz
Source: Rockefeller University
Contact: Katherine Fenz – Rockefeller University
Image: The image is credited to Neuroscience News
Original Research: Open access.
” A humanized NOVA1 splicing factor alters mouse vocal communications” by Robert B. Darnell et al. Nature Communications
Abstract
A humanized NOVA1 splicing factor alters mouse vocal communications
A central nervous system-expressing neuronal RNA-binding protein called NOVA1 is necessary for survival in mice and normal human development.
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 ( Nova1hu/hu ) and analyzed the molecular and behavioral consequences.
Although the I197V substitution had little to do with NOVA1’s RNA binding capacity, it had significant influence 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 , Nova1hu/hu , mice as pups and adults.
Our findings point to the possibility that this human-specific NOVA1 substitution may have occurred as a result of an ancient evolutionary selective sweep in a common ancestral group of Homo sapiens, possibly influencing the development of spoken language through differential RNA regulation during brain development.
