FOXP2: To speak or not to speak?

Preface:
Do you always believe what you hear? Several years ago do you remember the reports on the news about the famous diet pill Fen-phen. Amazing: a pill I can take to lose weight and increase my chances for pulmonary hypertension and heart value regurgitation! Well, maybe the pill isn’t so amazing. Do you also hear about the discovery of new genes? Genes for memory, muscular dystrophy, obesity, and the list could go on and on…. But how do you know popular press jargon is consistent with the scientific findings? Here is a comparison of literature published concerning FOX2P, a gene that is correlated with orofacial movements. The gene encodes a forkhead-domain transcription factor 715 amino acids long. It is the first gene to be correlated with speech and language (1).

Popular Press:

Academic Press: Daily Insight (an adjunct to Science Magazine) Posted: 3, October 2001
First ‘speech gene’ identified
Summary: Researchers identified a gene for speech out of a British family (KE) with known speech difficulties, particularly in pronunciation, word order and comprehension. The break through for the gene identification came when a five year old boy with a translocation at chromosome 7 displayed similar speech difficulties. The translocation occurred in the middle of a gene dubbed FOXP2. The article cautions that the gene should not be correlated with language just yet since the disorder involves motor functions (2).

 

Academic Press: Daily Insight (an adjunct to Science Magazine) Posted: 14 August 2002
“Speech Gene” a Debut Time to Modern Humans
Summary: The article highlights a letter published in nature that explains the evolution of FOX2P in various species, particularly primates and humans. A model is proposed that suggests that the human gene diverged 200,000 years ago. Apparently the gene has only three amino acid differences from its predecessor in the mouse, suggesting a highly conserved sequence. The article also suggests that dating analysis remains “fraught with uncertainty” in addition to the speculation that language is a cause behind the migration of humans (3).

 

BBC: Science and Nature Posted: 14 August 2002
First Language Gene Discovered
Summary: The sensational article states that a “mistake” in the DNA is responsible for a language disorder. The gene responsible is FOX2P, “the first definitely linked (gene) with human language”. The article also claims that without it (FOX2P) language may have never evolved. The article highlights additional speculation on behalf of the researchers (4).

 

CNN.com Posted: 15 August 2002
Study: Apes lack gene for speech
Summary: The article makes claims similar to the aforementioned articles including the introduction of FOXP2 200,000 years ago. Scientists have been studying the protein the gene in humans. The article focuses on the genes ability to make humans “distinct” from other species while identifying the KE family and the disorder responsible for the gene. The CNN article is the first to indicate that two normal FOXP2 genes are required for correct speech. The article also raises the debate concerning language in different species. Do dolphin and whales speak to each other? (5)

 

Time Magazine Posted: 26 August 2002
Origins: A Gene for Speech
Summary: A gene linked to a family with a speech disorder is now believed to play an evolutionary role in human development. It appears that a 200,000 year old mutation may be the reason humans speak today. (6)


Scientific Letters:

Nature Posted: 4 October 2001
A forkhead-domain gene is mutated in a speech and language disorder
Summary: Researchers isolated two different mutations in a gene believed play a role in speech development FOXP2. A five year old boy with a translocation from chromosome five at 7q31 had a speech disorder. An autosomal dominant point mutation was found in the same region for the KE family, a British family with a history of a speech disorder.
FOXP2 is a transcription factor with a polyglutamine tract and a forkhead DNA binding domain. Researchers speculate that the transcription factor is a crucial element to the development of speech. (7)

Nature Posted: 22 August 2002
Molecular evolution of FOXP2, a gene involved in speech and language
Summary: Two normal copies of FOXP2 are necessary for language articulation.
Alterations in amino acid sequence and nucleotide polymorphisms implement FOXP2 selection for human evolution. The gene encodes a protein of 715 amino acids and is classified as a forkhead transcription factor.
Only three amino acids differ between comparisons of human and mouse FOXP2. “Two of the three amino-acid differences between humans and mice occurred on the human lineage after the separation from the common ancestor with the chimpanzee.” A change in amino acid 325 suggests a potential site for phosphorylation by a protein kinase. A study of 91 individuals revealed only one discrepancy in amino acid sequence. Researchers hypothesized that the gene is responsible for “orofacial movements.” They continue to speculate that the gene may be responsible for the “expansion of modern humans”. (1)


Other Scientific Letters:
Other studies suggest possible implications and structural motifs for the FOXP2 gene. A letter published in human genetics suggests that FOXP2 also contains a “zinc finger motif” and could be responsible for other “nuropsychiatric disorders.” FOXP2 is 603 kb long with various exons and splice variants (8). Searching PubMed for other letters under the key words “speech gene” found articles trying to link FOXP2 to children with speech difficulties and autism.

What do I believe? What should I read?

The popular press is inherently sensational. But in this case, the articles published in the BBC, Time, Academic Press and CNN are fairly accurate. However, the articles do latch on to several key points published in Nature concerning the evolution of FOXP2. For example, nearly every article mentioned that FOXP2 evolved 200,000 years ago. The articles neglected to mention that the authors in nature created a statistical model for gene selection that suggested that FOXP2 evolved 120,000 to 200,000 years ago. The articles also stress that the expansion of humans was associated with speech development, even thought this is purely speculation on the authors behalf. CNN and the Academic Press were the only publishers who provided contrary points or explicitly discussed the authors’ speculation in the conclusion.
What is interesting is that a point mutation or translocation results in a dominant mutation and speech disorder. The authors in nature point out that FOXP2 is highly conserved and humans and mouse FOXP2 proteins differ by 3 amino acids. FOXP2 is expressed in fetal and adult brain; it is also a member of a family of transcription factors, which regulate embryogenesis. Different isoforms have been isolated for the gene as well. So is one gene responsible for speech? Probably not. FOXP2 is the first gene to be correlated with speech and probably many others will follow suit.

References:

1. Wolfgang, E.; Prezeworski, M.; et al. Molecular Evolution of FOXP2, a gene involved in speech and language. Nature. Vol. 418. 22 August 2002. 869-872.

2. Balter, Michael. "First 'Speech Gene' identified". Academic Press: Daily Insight. Science. 3 October 2001. http://www.academicpress.com/inscight/10032001/grapha.htm

3. Balter, Michal. "'Spech Gene' A Debut Timed to Modern Humans". Academic Press: Daily Insight. Science. 14 August 2002. http://www.academicpress.com/inscight/08142002/grapha.htm

4. Briggs, Helen. "First Language Gene discovered". BBC. 14 August 2002. http://news.bbc.co.uk/1/hi/sci/tech/2192969.stm

5. Walton, Marsha. "Study: Apes Lack Gene for Speech". Cnn Sci-Tech. 15 August 2002. http://www.cnn.com/2002/TECH/science/08/15/coolsc.speech/index.html

6. Stolze Cornella; Blaine Greteman. "Origins: A Gene for Speech" Time magazine. 26 August 2002.

7. Lai, C. S.; Fisher S. E.; et al. A forkhead-domain gene in a severe speech and language disorder. Nature. Vol. 413. No. 6855: 465-466.

8. Bruce, H. A.; Margolis, R. L. FOXP2: novel exons, splice variants, and CAG repeat length stability. Human Genetics. Vol 111. No. 2: 136-144.


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