Find your way in the dark with FoxP2

It's the wonder gene that makes the mute birds sing, the mute mice squeak and the mute Neandertals talk. And now, we find out that it fights mosquitoes, too. Echolocation has selected for a variety of FoxP2 mutations in different lineages of bats, according to this PLoS ONE study by Gang Li and colleagues:

FoxP2 is a transcription factor implicated in the development and neural control of orofacial coordination, particularly with respect to vocalisation. Observations that orthologues show almost no variation across vertebrates yet differ by two amino acids between humans and chimpanzees have led to speculation that recent evolutionary changes might relate to the emergence of language. Echolocating bats face especially challenging sensorimotor demands, using vocal signals for orientation and often for prey capture. To determine whether mutations in the FoxP2 gene could be associated with echolocation, we sequenced FoxP2 from echolocating and non-echolocating bats as well as a range of other mammal species. We found that contrary to previous reports, FoxP2 is not highly conserved across all nonhuman mammals but is extremely diverse in echolocating bats. We detected divergent selection (a change in selective pressure) at FoxP2 between bats with contrasting sonar systems, suggesting the intriguing possibility of a role for FoxP2 in the evolution and development of echolocation. We speculate that observed accelerated evolution of FoxP2 in bats supports a previously proposed function in sensorimotor coordination.

This gene is a great example of the way that comparative and experimental genetics contribute to our understanding of genetic networks. FoxP2 was recognized as important to human language performance from traditional pedigree studies.

Then, comparative genetics showed that humans differ from chimpanzees at two amino acid sites, despite the fact that the sequence is strongly conserved in most vertebrates. That suggested positive selection on the gene sometime during human evolution.

Additionally, the distribution of variation around the gene in humans suggested that an adaptive variant swept to fixation sometime during the last 200,000 years. That is the only element of the story so far that has involved the genetics of populations, as opposed to phylogenetic comparisons.

These findings prompted experimental genetic work. FoxP2 knockout mice were created, and these mice vocalize less, in particular as juveniles.

Studies of the expression of FoxP2 during brain development show that, along with the similar FoxP1, it regulates the expression of other genes in ways that may regulate the integration between sensory information and movement. Humans share these expression patterns with songbirds (Teramitsu et al. 2004), and song-learning birds like zebra finches appear to have different patterns of FoxP2 expression from non-learning birds (Haesler 2004). Dolphins and whales also share amino acid substitutions relative to non-cetaceans, flanking one of the functional changes in the human sequence (Webb and Zhang 2005).

Still, we don't know exactly what the gene does, or why it is so conserved in non-vocal-learning species of vertebrates. It appears to interact with FoxP1 during cortical development, possibly guiding neuron migration. But as yet it is unclear what genes it may regulate, or what gives rise to its expression pattern. More experimental analysis of the knockouts may help unravel these problems, or statistical analysis of expression. Since it has changed recently in human evolution, we can expect that some of the genes in its interaction network probably changed as well.

References:

Enard W, Przeworski M, Fisher SE, Lai CS, Wiebe V, Kitano T, Monasco AP, Pääbo S. 2002. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418:869-872.

Haesler S, Wada K, Nshdejan A, Morrisey EE, Lints T, Jarvis ED, Scharff C. 2004. FoxP2 expression in avian vocal learners and non-learners. J Neurosci 24:3164-3175. doi:10.1523/JNEUROSCI.4369-03.2004

Li G, Wang J, Rossiter SJ, Jones G, Zhang S. 2007. Accelerated FoxP2 Evolution in Echolocating Bats. PLoS ONE 2(9): e900. doi:10.1371/journal.pone.0000900

Teramitsu I, Kudo LC, London SE, Geschwind DH, White SA. 2004. Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction. J Neurosci 24:3152-3163. doi:10.1523/JNEUROSCI.5589-03.2004

Webb DM, Zhang J. 2005. FoxP2 in song-learning birds and vocal-learning mammals. J Hered 96:212-216. doi:10.1093/jhered/esi025