Saturday 10 January 2009

Gene of the Week: FOXP2

The Gene of the Week is a new feature that I've decided to bring to my blog. Each weekend I'll (try to) write a bit about a gene and it's related gene product that I think is pretty cool.

This week's gene is FOXP2, a gene that has been implicated as having a role in the development of language skills, and is likely to have played a major role in shaping the early evolution of Homo sapiens.

FOXP2 is a member of the Forkhead Box gene family (called "forkhead" after the prominent helix-turn-helix motif that resembles a forked head). It's located (in humans) on the q-arm of chromosome 7, and has a 2285bp transcript. It's gene product, the FOX P2 protein, is fairly large, at 715 amino acids in length. The gene is required for the proper development of the brain and the lungs, but where the gene shines is it's involvement with speech and related processes.

The history of the gene is actually quite interesting. Around 1990, a family known simply as the KE family, caught the scientific community's attention. The family was of particular interest because, over the previous three generations, around half of the family members developed severe problems with speaking - to a point that their speech was quite incomprehensible and they had to rely on sign language to communicate - as well as other physical and mental handicaps. A pedigree of the family and the disorder showed a pattern of inheritance suggestive of a mutation in a single, autosomal dominant gene.

It was not until 1998, when Fisher et al.1 did a linkage study and narrowed the location of the gene to a small region of chromosome 7 (7q31), and named the hypothetical gene SPCH1. Three years later, in 2001, Lai et al.2 made an interesting discovery. Working with a patient that exhibited a similar to that of the KE family, they discovered that the patient had a chromosomeal translocation affecting chromosome 7. In fact, the break point of the translocation was in the very region that Fisher and colleagues pinpointed in 1998. Going back to the KE family, the team found that the same gene that was broken in their patient had a point mutation in all of the affected members of the KE family and was not found in any of the unaffected members or control groups. In effect, they had found the gene that was causing the disorder in the KE family. The popular media caught wind of this discovery and, unsurprisingly, overexaggerated the finding with claims of a "gene for language", implying that this was a gene unique to humans that allowed us to talk - a claim that was blatantly false.

The gene that Lai and fellows found was a member of the FOX gene family - FOXP2.

Since then, lots of work has been done on the FOXP2 gene. It's been shown to affect vocalization in mice pups, song learning in finches, and even in the development of echo-location in bats. It has also been found that the gene is widely conserved, from fish to alligators to humans. However, what makes the gene particularly interesting from an evolutionary standpoint is that the human form of the gene is a bit different from the rest: it differs from the form of the gene found in other primates by two amino acids. It is speculated by some researchers that this difference is what lead to the development of language in humans, though a mechanism for this is yet unknown. Other researchers are of a different mind, claiming that the two amino acid difference is unlikely to have resulted in the development of language, but rather, a difference in gene regulation - when and where the human form of FOXP2 is expressed - is a more likely origin.

Much work remains to be done on FOXP2. It is a known transcription factor, but the genes it regulated are still unknown. Investigations into its role in evolution will undoubtedly continue. Be sure to keep your eye out for developments in this gene; it's bound to shed some light on the recent evolution of our species.

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1. Fisher et al, Nat Genet 18, 168 –170 (1998)
2.
Lai et al, 'A forkhead-domain gene is mutated in a severe speech and language disorder' Nature 413, 519 - 523 (2001)

For further reading and more details, see:
http://www.evolutionpages.com/FOXP2_language.htm
http://en.wikipedia.org/wiki/FOXP2
http://www.genenames.org/data/hgnc_data.php?match=FOXP2
http://www.wikigenes.org/e/gene/e/93986.html
http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nuccore&id=219518945

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