FOXP2 is a member of the large FOX family of transcription factors. Information from known human mutations and mouse studies suggest that FOXP2 regulates genes involved in the development of tissues such as brain, lung, and gut. The exact identity of the genes FOXP2 regulates is still not known, however.
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. For example:
Different studies of FOXP2 in songbirds suggest that FOXP2 may regulate genes involved in neuroplasticity: During song learning FOXP2 is upregulated in brain regions critical for song learning in young zebra finches. Knockdown of FOXP2 in Area X of the basal ganglia of these birds results in incomplete and inaccurate song imitation. Similarly, in adult canaries higher FoxP2 levels also correlate with song changes. In addition, levels of FOXP2 in adult zebra finches are significantly lower when males direct their song to females than when they sing song in other contexts. Differences between birds which are learning songs and those which are not have been shown to be caused by differences in FOXP2 gene expression, rather than differences in the amino acid sequence of the FOXP2 protein.
FOXP2 has also been implicated in the development of bat echolocation. A recent extraction of DNA from Neanderthal bones indicates that Neanderthals had the same version (allele) of the FOXP2 gene that is known to play a role in human language.
The FOXP2 protein sequence is highly conserved. Similar FOXP2 proteins can be found in songbirds, fish, and reptiles such as alligators. Aside from a polyglutamine tract, human FOXP2 differs from chimp FOXP2 by only two amino acids, mouse FOXP2 by only 3 amino acids, and zebra finch FOXP2 by only 7 amino acids. Some researchers have speculated that the two amino acid differences between chimps and humans led to the evolution of language in humans. Others, however, have been unable to find a clear association between species with learned vocalizations and similar mutations in FOXP2. Both human mutations occur in an exon with no known function. It is also likely, based on general observations of development and songbird results, that any difference between humans and non-humans would be due to regulatory sequence divergence (affecting where and when FOXP2 is expressed) rather than the two amino acid differences mentioned above.
The search for the gene was initially started as a result of the investigations into the KE (or K) family. Certain members of this family suffered from an inherited speech and language disorder and living members stretched back three generations. Closer inspection of the family revealed the disorder to be autosomal dominant.
A scan was performed of the genome of the affected and some of the unaffected family members. This initial scan limited the affected region to a spot on chromosome 7, which the team called "SPCH1". Sequencing of this region was done with the aid of bacterial artificial chromosome clones. At this point, another individual was located who had a similar disorder but was unrelated to the family. The genome of this individual was mapped and it was discovered that there was a break in chromosome 7.
Further investigation discovered a point mutation in this chromosome. Sequenced and analysed, this is now referred to as the FOXP2 gene.