Image credit: Nikolett Emmert/Unsplash

In a quest to understand complex speech, scientists inserted what’s been dubbed a human “language gene” into mice. Remarkably, the genetic tweak had a profound impact on the little rodents’ ability to squeak, revealing astonishing clues about the evolution of vocal communication. Mouse pups that had the human version of the language gene showed different vocalization patterns from their buddies with the usual version mice have……Continue reading….

By: Tom Hale

Source: IFLScience

.

Critics:

FOXP2 is a transcription factor with multiple functions among which is that it plays a role in the development of neural circuits that are involved in speech and language. It functions by regulating the genes that influence factors such as differentiation of neurons, communication between neurons, and synaptic plasticity. Additionally, FOXP2 helps coordinate the complex movements required for speech; consequently, it is highly expressed in brain regions associated with motor control and language processing, including the basal ganglia and cerebral cortex.

Mutations in FOXP2 have been linked to a rare genetic speech and language disorder known as childhood apraxia of speech, which is recognized to cause impaired articulation and difficulty with grammar and comprehension. In mouse models, mutations in FOXP2 have led to deficits in motor learning and impaired synaptic plasticity, highlighting its importance in neural function.

Furthermore, mice expressing a “humanized” version of the gene show significant alterations in cortico-basal ganglia circuitry. Additionally, in songbird models, knockdown of FOXP2 disrupts vocal learning, resulting in incomplete and inaccurate song imitation. Thesefindings collectively illustrate that FOXP2 is essential for the development of the neural mechanisms underlying complex vocal communication.

The FOXP2 gene has been implicated in several cognitive functions including; general brain development, language, and synaptic plasticity. The FOXP2 gene region acts as a transcription factor for the forkhead box P2 protein. Transcription factors affect other regions, and the forkhead box P2 protein has been suggested to also act as a transcription factor for hundreds of genes. This prolific involvement opens the possibility that the FOXP2 gene is much more extensive than originally thought.

Other targets of transcription have been researched without correlation to FOXP2. Specifically, FOXP2 has been investigated in correlation with autism and dyslexia, however with no mutation was discovered as the cause.  One well identified target is language. Although some research disagrees with this correlation, the majority of research shows that a mutated FOXP2 causes the observed production deficiency

There is some evidence that the linguistic impairments associated with a mutation of the FOXP2 gene are not simply the result of a fundamental deficit in motor control. Brain imaging of affected individuals indicates functional abnormalities in language-related cortical and basal ganglia regions, demonstrating that the problems extend beyond the motor system.

Mutations in FOXP2 are among several (26 genes plus 2 intergenic) loci which correlate to ADHD diagnosis in adults – clinical ADHD is an umbrella label for a heterogeneous group of genetic and neurological phenomena which may result from FOXP2 mutations or other causes. A 2020 genome-wide association study (GWAS) implicates single-nucleotide polymorphisms (SNPs) of FOXP2 in susceptibility to cannabis use disorder.

It is theorized that the translocation of the 7q31.2 region of the FOXP2 gene causes a severe language impairment called developmental verbal dyspraxia (DVD) or childhood apraxia of speech (CAS) So far this type of mutation has only been discovered in three families across the world including the original KE family. A missense mutation causing an arginine-to-histidine substitution (R553H) in the DNA-binding domain is thought to be the abnormality in KE.

This would cause a normally basic residue to be fairly acidic and highly reactive at the body’s pH. A heterozygous nonsense mutation, R328X variant, produces a truncated protein involved in speech and language difficulties in one KE individual and two of their close family members. R553H and R328X mutations also affected nuclear localization, DNA-binding, and the transactivation (increased gene expression) properties of FOXP2.

These individuals present with deletions, translocations, and missense mutations. When tasked with repetition and verb generation, these individuals with DVD/CAS had decreased activation in the putamen and Broca’s area in fMRI studies. These areas are commonly known as areas of language function. This is one of the primary reasons that FOXP2 is known as a language gene.

They have delayed onset of speech, difficulty with articulation including slurred speech, stuttering, and poor pronunciation, as well as dyspraxia. It is believed that a major part of this speech deficit comes from an inability to coordinate the movements necessary to produce normal speech including mouth and tongue shaping. Additionally, there are more general impairments with the processing of the grammatical and linguistic aspects of speech.

These findings suggest that the effects of FOXP2 are not limited to motor control, as they include comprehension among other cognitive language functions. General mild motor and cognitive deficits are noted across the board. Clinically these patients can also have difficulty coughing, sneezing, or clearing their throats. While FOXP2 has been proposed to play a critical role in the development of speech and language, this view has been challenged by the fact that the gene is also expressed in other mammals as well as birds and fish that do not speak.

It has also been proposed that the FOXP2 transcription-factor is not so much a hypothetical ‘language gene’ but rather part of a regulatory machinery related to externalization of speech. Other researchers have argued that understanding of FOXP2 and its influence upon language disorders should be considered in the context of its interaction with other co-active genes in the human genome. The FOXP2 gene is highly conserved in mammals.

The human gene differs from that in non-human primates by the substitution of two amino acids, a threonine to asparagine substitution at position 303 (T303N) and an asparagine to serine substitution at position 325 (N325S). In mice it differs from that of humans by three substitutions, and in zebra finch by seven amino acids. One of the two amino acid differences between human and chimps also arose independently in carnivores and bats. Similar FOXP2 proteins can be found in songbirds, fish, and reptiles such as alligators.

DNA sampling from Homo neanderthalensis bones indicates that their FOXP2 gene is a little different though largely similar to those of Homo sapiens (i.e. humans). Previous genetic analysis had suggested that the H. sapiens FOXP2 gene became fixed in the population around 125,000 years ago. Some researchers consider the Neanderthal findings to indicate that the gene instead swept through the population over 260,000 years ago, before our most recent common ancestor with the Neanderthals.

Other researchers offer alternative explanations for how the H. sapiens version would have appeared in Neanderthals living 43,000 years ago. According to a 2002 study, the FOXP2 gene showed indications of recent positive selection. Some researchers have speculated that positive selection is crucial for the evolution of language in humans. Others, however, were unable to find a clear association between species with learned vocalizations and similar mutations in FOXP2.

Experts warn vaping alters genes, fruit flavors do most damage  21:20 Mon, 01 Jun