Chapter 4 MECHANISMS OF LANGUAGE Grammar at work Journalists say that it is not news when a dog bites a person; When a person bites a dog, it’s something new. And this is precisely the essence of the linguistic instinct: language communicates something new. Chains

Chapter 11 THE BIG BANG The Evolution of Language An elephant's trunk is six feet long and one foot thick and contains sixty thousand muscles. With the help of their trunk, elephants can uproot trees, stack logs, or carefully place them in the desired position when

The Role of Language in the Origin of Consciousness According to Julian Jaynes (1976), the unity of personality that Gazzaniga wrote about is a surprisingly recent development in the history of the human race. Jaynes believes that consciousness appeared in humans only about three thousand years ago,

George Berkeley Theory of vision, or visual language, showing the immediate presence and providence of the deity; defended and explained. In response to the anonymous author<…>6. The fact that atheistic principles have taken deep roots and spread further than

Speech is a brain function that is unique to humans. But did the Neanderthal possess it? Latest "reads" of the amino acid sequence protein product the speech gene suggests that, at least, the inhabitants of the Neander River valley, a tributary of the Rhine, did not have developed speech.

It all started more than 10 years ago, when a KE family was described in England, three generations of which suffered from speech and language disorder in the more general sense of the word. Not only did they say “Koykogo Street,” they also changed the order of words in the sentence, which is simply unacceptable in English. At the same time, their level of intelligence as a whole did not suffer particularly.

Chromosomal studies of family members made it possible to identify the zone in which the defective gene was supposedly located. The researcher who first described the KE family also described a 5-year-old boy with similar speech impairments. Chromosome analysis made it possible to identify a translocation (i.e., “jump”) of a section of the 5th chromosome to the 7th, as a result of which one of the genes simply “broke” in half.

The gene was named "Speech", which means "speech" in English. It encodes a protein that is an important regulator of gene activity. Damage to the gene leads to a point replacement of arginine with histidine in primary structure squirrel.

Magazine article Nature, dedicated to the description of the speech gene, was published in October 2001. And in mid-August 2002, the magazine again turned to this topic, publishing an article by S. Paabo from the Leipzig Institute of Evolutionary Anthropology.

At one time, Paabo became famous for isolating and sequencing the DNA of the mummy. This time he sequenced the proteins of the speech gene in great apes, humans and rhesus monkeys. The ancestors of apes and macaques diverged from each other about 70 million years ago. Mathematical analysis amino acid sequences showed that the human version of the speech gene was fixed 120 thousand years ago and not earlier than 200 thousand years ago.

What advantages did the human form of the gene provide? It is quite possible that it was the development of speech communication as the most information-intensive and requiring the least amount of energy that became the advantage that allowed to modern man"cope" with their Neanderthal brothers.

Based on materials

Nature, 2001, No. 6855, p. 519
Science, 2002, No. 5540, p. 32; No. 5584, r. 1105

If speech is an evolutionary acquisition of man, it must also have a genetic basis. It is a common fact that only 1% of us differ from our closest relative among the great apes. genetic material. It seems like quite a bit, but it’s not so easy to sort through the entire genome in search of differences of interest. This approach has not yet brought any stunning discoveries: most of the differences discovered turn out to be functionally neutral. Therefore, the genetics of the “most human” characteristics, which include speech, remain largely unknown. However, another approach is available to us: determining the genetic basis of pathology in patients with a violation of the function of interest to us. Everything that is known today about the genetics of speech was revealed in this way.

KE family

In the 1990s, one came to the attention of scientists British family, which is called KE in the literature. In this family, a rather severe speech disorder occurred in three generations, and it was inherited as an autosomal dominant trait. This discovery caused a huge stir, with some scientists rushing to the conclusion that we were close to discovering a “speech gene” or even a “grammar gene.” Long before biology could confirm or refute this, Noam Chomsky insisted that there was some kind of innate language acquisition device, already “tailored” for universal grammar, “knowing” in advance general principles language and only waiting for a specific language environment. But if the mechanism is innate, it will have a genetic basis - and all the eyes of those hoping to find these reasons turned to the KE family.

First, a neuropsychological examination was performed. It turned out that all family members, including those who did not suffer speech disorder, IQ was below average. That is, firstly, the speech disorder described is not entirely specific, and some manifestations may be due to mental retardation. Secondly, special speech tests also did not confirm the hypothesis that the ability to use grammatical rules was affected. Rather, the patients had difficulties with coordination of movements and control of the muscles of the orofacial zone. In this case, the disorder had the nature of apraxia, that is, a violation of the development of motor programs, but specifically in relation to speech; Since then it has been called accordingly: childhood apraxia of speech. But it is interesting that defects were found not only in oral speech, but also in written speech, and also involved speech perception (it is known that reference to our own, internal motor programs is necessary for the perception of someone else's speech). Neuroimaging studies showed that there was a disruption in brain development that resulted in morphologically recorded changes in the size of certain structures, including the subcortical nuclei and cerebellum.

However, the connection with speech function was obvious, and this was the only “genetic clue” that was in the hands of scientists. At the end of the nineties, the search began for genetic structures that would cause speech disorders in the KE family. First, they discovered that chromosome 7 was different in structure, then - its specific section where the gene was supposedly localized. It was named SPCH1 - and, finally, using data from another clinical case, the gene itself was discovered - FOXP2.

FOXP2 in evolution

The FOXP2 product is a transcription factor, that is, it regulates the expression of other genes. It directly binds to the region of DNA containing these genes, which affects the likelihood of their transcription. A special feature of this protein is its structural motif – a fork-shaped domain (forkhead-box, or FOX domain for short), which binds to DNA.

The gene appears to be involved in functions more important than speech. This is indicated by the absence in the human population of individuals in whom both copies of FOXP2 were damaged. In addition, evolutionary studies have found that this gene is highly conserved in mammals: in chimpanzees, gorillas and rhesus macaques, it differs by only one amino acid substitution from its mouse orthologue. The corresponding monkey gene differs from the human ortholog by two amino acid substitutions. However, more significant differences are revealed in the pattern of expression: for example, in humans, the repeating sequence of glutamine molecules varies in length, but in chimpanzees this feature is not observed. In addition, it was noted that in humans, compared to probabilistic calculations, the number of active substitutions is higher than silent ones (silent mutations do not lead to changes in the amino acid sequence). This indicates that there was selection in favor of the human variant of the FOXP2 gene, that is, it could be at least one of the genes that determined the emergence of language abilities in evolution.

Analysis of the variability of the FOXP2 intron in different human populations made it possible to approximately estimate the time of appearance of the mutation that led the gene to modern look. This happened about 220 thousand years ago, that is, during the formation of man of the modern anatomical type (CHSAT), Homo Sapiens. However, it later turned out that FOXP2 also looked the same in Neanderthals, that is, the gene should have appeared during the existence of the common ancestor of Neanderthals and ChSAT, about 300-400 thousand years ago. However, the dating methods themselves require additional verification.

FOXP2 in mice

The researchers' next step was to study the function of FOXP2, and since it differs in mice by only a few amino acid changes, they seemed like a useful model. Among the effects of Foxp2 knockout (in mouse version its spelling is slightly different) are related to vocalization: such animals spontaneously give voice less often - but they are controversial, and are far from in first place. During embryogenesis, the growth and branching of neurons is impaired in Foxp2 knockout mice, and the direction of axonal growth is distorted. Mice with the “switched off” gene live 3-4 weeks, slowly gain weight and do not

reach normal sizes, have multiple movement disorders, which is explained by delayed maturation of the cerebellum. In humans, there are no neurological symptoms associated with FOXP2 defects other than the mentioned cognitive deficits.

It is possible that the lethality of missing normal copies of the FOXP2 gene (and its homologue in mice) is related to its effects in other tissues, such as the heart and lung. The gene is mainly expressed in the deep layers of the cortex, Purkinje cells of the cerebellum and in medium-sized spiny neurons in the striatum.

Another experiment was to create in mice the same mutation in FOXP2, which led to the disease in the KE family (and also in a heterozygous state). The consequences of such a replacement have been studied in more detail at the tissue level. Synaptic plasticity in corticostriatal and cerebellar connections appears to be altered; in glutamatergic synapses of spiny neurons of the striatum, long-term depression was observed less frequently than normal. Accordingly, the level of basal activity of these neurons in electrophysiological studies was increased, which is consistent with the results of neuroimaging in the KEs themselves: she also demonstrated striatal dysfunction.

Research on FoxP2 in birds is interesting: although their version of the gene is more different from humans, its clear connection with vocalization has been demonstrated. The gene is highly expressed in the striatum, which is part of the neural network that mediates vocalization in songbirds. Using the zebra finch, it was possible to show that if gene expression is artificially reduced using molecular genetic methods, the chick learns its specific song incompletely and in a distorted form.

FOXP2 targets

If FOXP2 is a transcription factor, then genes that directly influence speech development should be among its targets. Several such genes are actually known:

– CNTNAP2 (Contactin-associated protein-like 2) encodes trans membrane protein CASPR2, which belongs to the neurexin superfamily and mediates cell-cell interactions. A connection between various mutations in this gene and autism, schizophrenia, epilepsy, and Tourette's syndrome has been demonstrated. All carriers of these mutations share common phenotypic features: mental retardation, seizures, autistic behavior and language impairment - and each of these features can range in severity from minor to disabling. The speech disorders we are interested in are manifested by a delay speech development, complete lack of speech and dysarthria. The most studied association of one of the SNPs (single nucleotide polymorphism) with specific language impairment (SLI) is a disease in which speech is impaired in the absence of hearing defects and autistic features. A high level of CNTNAP2 expression is observed in layers II-IV of the cortex of Broca's area and areas surrounding the Sylvian fissure.

– the SRPX2 and uPAR genes function in a complex, and FOXP2 regulates the expression of both. The SRPX2 gene is associated with Rollandic epilepsy and apraxia of speech; morphologically, such patients often exhibit microgyria in the area of ​​the Sylvian fissure. It was shown in mice that it is the expression of SRPX2 that affects the formation of excitatory synapses and spines, that is, a disruption in this link may be responsible for the corresponding effect of FOXP2 knockout in mice. The uPAR gene encodes the plasminogen activator receptor, which is involved in the effect of SRPX2.

– Among the genes whose expression is controlled by FOXP2 are candidate genes for autism, for example, MET or MEF2C. The function of MEF2C (myocyte enhancer factor 2C) is presumably to negatively regulate (i.e. suppress) the formation of dendritic spines and excitatory synapses in hippocampal neurons; the same thing happened in an experiment in a culture of striatal cells. Since FOXP2 reduces the expression of MEF2C, its dysfunction leads to the opposite effect, which is consistent with the above data: in FOXP2 knockout mice we see hyperactivity of striatal neurons. In ontogenesis, this leads to the formation of corticostriatal connections to a different extent than what occurs normally. The MET gene encodes a receptor tyrosine kinase that is involved in many processes during embryogenesis. Regarding neurogenesis, it is known that this gene is actively expressed in neuronal growth cones at early stages of development, and its activation involves the small GTPase Cdc42 in the process and stimulates neuronal growth, dendritic branching and spine formation. Inactivation of MET in the experiment led to the formation of altered neurons, whose structure corresponded to the early stages of maturation. If MET activation was prolonged during embryogenesis, this suppressed the formation and maturation of glutamatergic synapses. Attempts to manipulate the level of MET expression in prefrontal neurons have led to disruption of the formation of neural networks in which these neurons are usually involved.

– DISC-1 (Disrupted in Schizophrenia) gene was originally studied as possible reason schizophrenia, but is currently being studied for many other mental disorders, including affective, mental retardation, autism. Its functions are poorly understood, but it is believed that it is also required for synaptogenesis.

Other diseases, other genes

In addition to FOXP2 and its team, other genes are being discovered whose damage affects various aspects of speech. It is clear that only one gene, even if it is a transcription factor, could not entirely determine the development of language and give such a sharp turn to human evolution. Apparently this was slow and required many modifications.

Among children's mental disorders there is a special section devoted specifically to speech disorders. Since it is genetically determined pathology that often manifests itself in childhood, the genetic basis of specific childhood speech disorders has been studied quite well.

1. Developmental dyslexia (reading disability) – difficulties with pronunciation and reading that cannot be explained by others obvious reasons, such as low IQ or physical disabilities, or learning disabilities. Affects 5-10% of children school age, and difficulties persist into adulthood. There are often difficulties with understanding speech, which are revealed by more subtle tests.

In genome-wide studies, 9 regions of DYX1-9 were identified, which may be associated with the development of this disease. Three of them contain specific genes:

– In the DYX1 region – the DYX1C1 gene. The functions of this gene include neuronal migration and cytoskeletal organization. Postmortem studies of the brains of people with DYX1C1 mutations in the left hemisphere revealed mild malformations associated with neuronal and glial dystopia.

– In the DYX2 region there are genes KIAA0319 and DCDC2. The KIAA0319 gene encodes a membrane protein with a large extracellular domain that is required for neuronal adhesion. DCDC2 encodes one of the domains of doublecortin (a protein expressed by immature neurons, a marker of neurogenesis) and is required for cytoskeleton-mediated intracellular dynamics.

– In the DYX5 region there is the ROBO1 gene, which encodes a guiding receptor for axons crossing midline. Its mutations, accordingly, lead to the formation of dysfunctional interhemispheric connections.

2. Specific speech disorder - inability to master, not due to other reasons colloquial speech, which affects one of its important aspects: morphology, syntax, pragmatics or semantics. Speech reproduction, perception, and written language. The disease affects up to 7% of children aged 5-6 years. With age, the deficit is corrected, but even in adulthood, deviations in complex tests remain. We have already mentioned one of the candidate genes for this disorder, CNTNAP2. Two more were located on chromosome 16: CMIP and ATP2C2. CMIP encodes a protein that is part of the cytoskeleton and, except in CPP, its mutations are found in patients with autism. ATP2C2 encodes a calcium ATPase and is involved in the regulation cellular levels magnesium and calcium.

3. Childhood apraxia of speech is a disorder that was described at the beginning of the material; it was this disorder that helped discover the FOXP2 gene. However, it later turned out that only a small percentage of patients who meet the criteria for this disorder have damage specifically in the FOXP2 gene, that is, most cases of childhood apraxia of speech must be due to other reasons.

4. Sound pronunciation disorder – difficulties with the reproduction and correct use of speech sounds, which are most often manifested by omissions and substitutions of sounds that are significant for understanding the meaning. This phenomenon is very often observed in young children who are just learning to speak. It is considered pathological if it persists by the age of six - this happens in approximately 4% of cases. This disorder is quite difficult to differentiate from childhood apraxia and specific

speech disorder. May have a common genetic basis with dyslexia, since the most significant association is found with changes in the DYX5 region.

5. Stuttering – involuntary repetition and prolongation of syllables, pauses that disrupt the fluency of speech. It usually resolves with age, but about 20% of patients continue to stutter into adulthood. Semantic and grammatical characteristics speech, as a rule, is not impaired. A connection was found with three genes that are involved in object recognition for lysosome enzymes: GNPTAB, GNPTG and NAGPA. All three genes encode subunits of the enzyme N-acetyl-glucosamine-1-phosphotransferase, which is necessary for “marking” mannose-containing oligosaccharides and subsequent recognition by lysosomes. These genes may also be associated with a more serious disease than stuttering—mucolipidosis types 2 and 3.

There is also a known complex of genes MCPH and ASPM, defects in which lead to microcephaly. In such patients, language development does not exceed the level of a six-year-old child. However, they do have basic language abilities, which again brings us to the greater importance of the internal structure of the brain rather than its size. MCPH encodes the protein microcephalin, which is involved in cell cycle organization and DNA repair before division. The ASPM product is necessary for the construction of division spindles and ensures the symmetry of the resulting cells. Interestingly, defective variants of these genes are rare in Africa, where tonal languages ​​are common, and common (up to 30%) in Europe, where languages ​​of this type do not exist.