FOXP2 Explained
All in the Family
Our story begins in Britain in 1990. Sixteen members of a large, three-generational family, known by scientists as KE, exhibited severe orofacial dyspraxia, a condition that affects movement and coordination. Their speech was at times unintelligible, and they exhibited deficits in morphological production, struggling to inflect words for the simple past tense and the plural (Watkins, 2011). They were treated by a genetics clinic, and their story quickly attracted the attention of researchers. Hurst and colleagues (1990) established that dyspraxia was inherited – as opposed to derived from environmental factors – possibly even Mendelian, and outlined the case histories. Adding to the mystery, the researchers noted that intelligence and hearing were all normal.
The KE family and their symptoms were a source of debate throughout the 1990s. Towards the end of the decade, Fisher et al. (1998) identified a region on chromosome 7 which validated Hurst’s assertion that the impairments of KE were genetic. Within this region, the researchers identified a mutation in the gene in the affected KE members.
The big boom came in 2001. This was the year that Lai, Fisher, Hurst, and others coauthored their groundbreaking article investigating the mutation in the forkhead box family (a series of proteins that regulate and copy genes and are essential in the development of everything from motor control in the brain to immune system function (Jackson, et al., 2010)) in KE. They identified the specific mutations within affected individuals (Lai, et al., 2001). The implications were massive: The idea that a gene was responsible for the development of language, arguably the most precious faculty in the human species. The news was sensational, the gene was dubbed FOXP2, and the world of molecular studies in evolution, development, and cognition forever changed.
Big Genes, Big Brains
Simply stated, FOXP2 refers to a gene that provides the blueprint for a protein to act as a transcription factor – in other words, the protein then controls the creation of other genes within this forkhead box family by attaching to the DNA. This gene is expressed in the development of plasticity in the thalamic nuclei, striatum, globus pallidus, and more (Watkins, 2011). Further evidence shows that FOXP2 is implicated in the development of basal ganglia circuits, which play a role in language vocalizations (Xiao et al, 2021).
Other studies indicate that FOXP2 is implicated in the lateralization of the brain and in particular those structures associated with language usage. Ocklenburg (2013) noted that the majority of individuals have left-hemispheric language dominance and explored the possibility that these fronto-temporal networks were linked to FOXP2 polymorphisms. They write, “Taken together, these findings show that variation in FOXP2 modulates language lateralization, presumably by affecting temporal and temporo-parietal brain functions.”
Modern research has sometimes disagreed on the role of FOXP2 in other disorders. Though Ocklenburg and colleagues state that schizophrenia, autism spectrums, and dyslexia have all been connected to reduced language lateralization (2013), other researchers have found no association between FOXP2 impairments and schizophrenia (McCarthy et al., 2019).
Evolution Casts Its Shadow
FOXP2 is among the most conserved proteins in mammals (Krause et al., 2007). The most important fact about the expression of FOXP2 in humans, as language-driven animals, is that, despite the comparative conservation of this gene, it differs from our closest living relatives (chimpanzees) in two amino acid sites (Fisher, 2019).
In Good Company
We know that humans are not alone in possession of FOXP2. Studied in zebra finches and mice and observed in fish and reptiles, animals present a model for scientists to outline the potential dyspraxia without involving human subjects. Wohlgemuth (2014) examined a population of zebra finches, noting that the gene is consistent across vertebrates, appearing in the striatum, thalamus, and more. Knocking down the gene in the zebra finch affects the development of its basal ganglia and the ability to learn songs (Murugan et al., 2013).
Experiments involving mice are even more widespread. Mice can present with the same dyspraxia that affects the KE family. The result was that the mice were unable to sequence vocalizations, and more modern imaging techniques have spotlighted the characteristically observed impairments in the plasticity of the ganglia (Fisher, 2019). The situation could be even more dire: Mice lacking the alleles of FOXP2 typically died 21 days after birth (den Hoed et al., 2021).
The New Neandertal
The story of FOXP2 took another drastic turn in 2007. A team of researchers (including future Nobel-winning evolutionary geneticist Svante Pääbo) produced a paper outlining their recent discovery that Neandertals possessed humans’ mutation of the arginine-histidine substitutions of FOXP2 (Krause et al., 2007). With their discovery came the murmurings that Neandertals were linguistic creatures.
The first implication of this discovery is that genetic research is revolutionizing our understanding of our evolution and that of our ancestors and closest relatives, living or extinct. Extracting DNA from ancient remains using polymerase chain reactions (amplifying copies of a specific segment of DNA) is fraught with difficulties because conditions are of low quantity in remains of that age (Krause et al., 2007). The other huge implication is that the targeted gene appeared earlier in the evolutionary tree than had been previously assumed.
This begs the question of whether or not the mutation occurred in the common ancestor of humans and Neandertals or was transferred to the latter via reproduction – it having been long known that humans and Neandertals reproduced together (Villanea & Schraiber, 2019). Examining both patrilineal Y chromosomes and matrilineal mtDNA, Krause and team assert that the presence of the gene and its characteristic mutation was the result of a “selective sweep” – in other words, that the gene was a beneficial mutation in both humans and Neandertals.
The presence of the gene alone does not guarantee that Neandertals possessed language abilities equivalent to humans, but it is the backbone of the argument that they did indeed have an aptitude for language. Though Neandertals and their potential language are not the purview of this article, these mutations, coupled with recent anatomical evidence such as human-like hyoid bones (Hogenboom, 2013), act as another puzzle piece in the grand portrait of language origins.
To the Future
Language is a complex and powerful human phenomenon. With it, we can fashion lyrics, poems, jokes, letters, text messages, conversations, and even Faust or The Tale of Genji. It is among the attributes that make our species unique, but the origin of this faculty remains one of science’s greatest and most studied mysteries. With the pioneering research conducted by geneticists for the past thirty years, we are undeniably a step closer to understanding the molecular dimensions of language and the concrete genes and proteins that make up the human story.
It is crucial to note that, given all that inherent complexity, language likely cannot be explained with a single gene, but the advent of FOXP2 research has indicated that bioinformatics has a role to play in this indelible mystery, in this theater of evolution and intelligence. If we return to Fisher, who stated in Nature, “We need to embrace more complex accounts that involve changes of multiple genes” (Warren, 2018), we begin to fashion a story of language that potentially shows our communicative aptitude ranging from songbirds trilling to human grammar. It is perhaps ironic that what makes us unique as a species might also unite us with our animal peers and our ancient cousins.
Works Cited
den Hoed, J., Devaraju, K., & Fisher, S.E. (2021). Molecular networks of the FOXP2 transcription factor in the brain. EMBO Reports, 22.
Fisher, S.E., Vargha-Khadem, F., Watkins, K.E., Monaco, A.P., & Pembrey, M.E. (1998). Localization of a gene implicated in a severe speech and language disorder. Nature Genetics, 18, 168 – 170.
Hogenboom, M. (2013, December 20). Neanderthals could speak like modern humans, study suggests. CNN.
Hurst, J. A., Baraitser, M., Auger, E., Graham, F., & Norell, S. (1990). An extended family with a dominantly inherited speech disorder. Developmental Medicine and Child Neurology, 32(4), 352–355
Jackson, B.C., Carpenter, C. Nebert, D.W., & Vasiliou, V. (2010). Update of human and mouse forkhead box (FOX) gene families. Human Genomics, 4 (5), 345 – 352.
Krause, J., Lalueza-Fox, C., Orlando, L., Enard, W., Green, R.E., Burbano, H.A., Hublin, J., Hänni, C., Fortea, J., de la Rasilla, M., Bertranpetit, J., Rosas, A., & Pääbo, S. (2007). The derived FOXP2 variant of modern humans was shared with Neandertals. Current Biology, 17, 1908 – 1912.
Lai, C. S., Fisher, S. E., Hurst, J. A., Vargha-Khadem, F., & Monaco, A. P. (2001). A forkhead-domain gene is mutated in a severe speech and language disorder. Nature, 413(6855), 519–523.
McCarthy, N.S., Clark, M.L., Jablensky, A., & Badcock, J.C. (2019). No association between common genetic variation in FOXP2 and language impairment in schizophrenia. Psychiatry Research, 271, 590 – 597.
Murugan, M., Harward, S., Scharff, C., & Mooney, R. (2013). Diminished FOXP2 levels affect dopaminergic modulation of corticostriatal signaling important to song variability. Neuron, 80, 1464 – 1476.
