A single protein could boost the appearance of human language

Thus, a team of scientists from the Rockefeller University in New York, has found a new and intriguing genetic evidence: the variant of a protein that is only in Homo Sapiens and that could have helped the appearance of spoken language. In a newly published study in ‘Nature Communications‘, and under the direction of Robert Darnell and Yoko Tajima, the researchers discovered that, by introducing this exclusively human variant of the Nova1 protein, known as crucial for the development of neurons, the vocalizations of rodents were altered while They called each other.

The study also confirmed that this particular variant is not present in Neanderthals and Denisovanos, archaic humans who crossed with our ancestors, as demonstrated by the genetic inheritance of those species that still remains in many current humans. “This gene,” explains Darnell, “is part of a radical evolutionary change in modern first humans and hints possible ancient origins of spoken language. Nova1 can, indeed, a human language gene, although it is certainly only one of many specific genetic changes that humans show.

A long chain of adaptations

Our linguistic abilities are the result of a long series of anatomical adaptations of the vocal tract, and also of the action of our intricate neural networks. However, genetics underlying this important human capacity has never been fully understood. We believe, for example, that a genetic driver of language is the FOXP2 gene, which encodes a transcription factor involved in the early development of the brain. In fact, people with mutations in this gene exhibit serious speech defects, including the inability to coordinate lip and mouth movements with sound.

In addition, our species has Foxp2 with a series of amino acid variations that do not exist in other primates or mammals, although in the Neanderthals, which suggests that the variant arose in a common ancestor of both human lineages. However, some of these findings in FOXP2 are subject to dispute, and their function in the development of human language remains without being clear. And there it is precisely where Nova1 fits, which arises as a new candidate to play that role.

The Foxp2 gene, in effect, produces a protein, cloned and characterized for the first time in 1993 by Darnell himself, which is specific to neurons and is key to the development of the brain and neuromuscular control. The protein is found virtually identical in a wide range of the biosphere, from mammals to birds, but not in humans. Instead, we do have our own unique form, characterized by a single change of an amino acid in the 1977 (I197V) position in the protein chain.

Of course, according to the main author Yoko Tajima, I197V is not the only replacement of amino acids that distinguishes modern humans from other organisms. And some of them could also be necessary for the development of the brain. “Such changes,” says Tajima, “may have played important roles in the acquisition of characteristics that have contributed to the appearance, expansion and survival of Homo Sapiens.”

Darnell, then, has been investigating Nova1 since the early 1990s, when he and his colleagues first identified him as the trigger for an autoimmune neurological disorder called Poma, which can cause extreme motor dysfunction. Recently, however, cases have also begun to identify cases in which the genetic variants of Nova1 are associated with language difficulties. “Understanding Nova1,” says Darnell, “has been the greatest effort of my entire career.”

In the current study, the researchers resorted to gene editing tools to replace the common Nova1 protein, present in mice, with the human variant I197V. Then, they used advanced techniques to identify the union sites of Nova1 in the middle brain of the mouse.

Discoveries chain

The first remarkable discovery was that the human variant had no impact on neuronal development or motor control. That is, it operated exactly the same as the one it had replaced. But what was I doing then? The second significant finding gave scientists a clue: the union sites that were substantially affected by the human variant of the protein were in genes related to vocalization.

“We think, ‘Wow’,” says Darnell. We didn’t expect that. It was one of those really surprising moments in science ». Then, the Darnell laboratory joined its forces to those of the Rockefeller’s neurogenetic laboratory, directed by Erich D. Jarvis, who studies the molecular and genetic mechanisms that underlie vocal learning.

During the following years, both laboratories investigated the impact on the vocalizations of various ages mice in different contexts. And found altered vocal patterns between young of both sexes and adult males. «All babies mice,” says Darnell – emit ultrasonic chillidos to their mothers, and language researchers classify the various shrieks as four ‘letters’: S, D, U and M. We discover that the chillidos emitted by mice with the variant I197V Specific humans, were different from those of wild type mice. Some of the ‘letters’ had changed.

The researchers also found similar patterns when studying adult male mice calls when exposed to females in heat. Those mice, says Darnell, ‘spoke’ in a different way to females. “It is easy to imagine how such changes in vocalization could have a deep impact on evolution.”

The human element

The potential influence of I197V in human evolution became the following objective of scientists. To confirm that the variant was not in our closest human relatives, Darnell and his team compared eight human genomes with three Neanderthal genomes and one from Denisovano. As expected, both archaic relatives, from whom it is believed that we separated about 250,000-300,000 years ago, had the same Nova1 protein as all non-human animals.

Later, they examined 650,058 modern human genomes in the DBSNP database, a catalog of variations in short sequences extracted from people around the world. If there was an alternative to I197V, it would certainly be there. But it turned out that of those 650,058 people, all but six, who had the archaic variant, possessed the human variant.

“Our data – Darnell proceeds – show that an ancestral population of modern humans in Africa developed the human variant I197V, which later became dominant, perhaps because it conferred advantages related to vocal communication. That population then left Africa and extended all over the world.

The investigation, of course, is not yet ended, and in the future the Darnell laboratory will investigate how Nova1 regulates the function of language. “We believe,” he says on the other hand, “to understand these problems will provide important information about how the brain operates during vocal communications, and how its deregulation leads to certain disorders. Our discovery could have clinical relevance in many ways, ranging from development disorders to neurodegenerative diseases.