[tt] NS: The evolutionary story of the 'language gene'

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The evolutionary story of the 'language gene'
http://www.newscientist.com/article.ns?id=mg19926691.800&print=true
13 August 2008
Ed Yong

IMAGINE an orchestra full of eager musicians which, thanks to an
incompetent conductor, produces nothing more than an unrelieved
cacophony. You're starting to appreciate the problem faced by a
British family known as KE. About half of its members have severe
difficulties with language. They have trouble with grammar, writing
and comprehension, but above all they find it hard to coordinate the
complex sequences of face and mouth movements necessary for fluid
speech. Thanks to a single genetic mutation, the conductor cannot
conduct, and the result is linguistic chaos. In 2001, geneticists
looking for the root of the problem tracked it down to a mutation in
a gene they named FOXP2. Normally, FOXP2 coordinates the expression
of other genes, but in affected members of the KE family, it was
broken.

It had long been suspected that language has some basis in genetics,
but this was the first time that a specific gene had been implicated
in a speech and language disorder. Overeager journalists quickly
dubbed FOXP2 "the language gene" or the "grammar gene". Noting that
complex language is a characteristically human trait, some even
speculated that FOXP2 might account for our unique position in the
animal kingdom. Scientists were less gushing but equally excited -
the discovery sparked a frenzy of research aiming to uncover the
gene's role.

Several years on, and it is clear that talk of a "language gene" was
premature and simplistic. Nevertheless, FOXP2 tells an intriguing
story. "When we were first looking for the gene, people were saying
that it would be specific to humans since it was involved in
language," recalls Simon Fisher at the University of Oxford, who was
part of the team that identified FOXP2 in the KE family. In fact,
the gene evolved before the dinosaurs and is still found in many
animals today: species from birds to bats to bees have their own
versions, many of which are remarkably similar to ours. "It gives us
a really important lesson," says Fisher. "Speech and language didn't
just pop up out of nowhere. They're built on very highly conserved
and evolutionarily ancient pathways."

The first team to compare FOXP2 in different species was led by
Wolfgang Enard from the Max Planck Institute for Evolutionary
Anthropology in Leipzig, Germany. In 2001, they looked at the
protein that FOXP2 codes for, called FOXP2, and found that our
version differs from those of chimpanzees, gorillas and rhesus
macaques by two amino acids out of a total of 715, and from that of
mice by three. This means that the human version of FOXP2 evolved
recently and rapidly: only one amino acid changed in the 130 million
years since the mouse lineage split from that of primates, but we
have picked up two further differences since we diverged from
chimps, and this seems to have happened only with the evolution of
our own species at most 200,000 years ago (Nature, vol 418, p 869).

The similarity between the human protein FOXP2 and that of other
mammals puts it among the top 5 per cent of the most conserved of
all our proteins. What's more, different human populations show
virtually no variation in their FOXP2 gene sequences. Last year,
Enard's colleague Svante Pääbo made the discovery that Neanderthals
also had an identical gene, prompting questions over their
linguistic abilities (see "Neanderthal echoes").

"People sometimes think that the mutated FOXP2 in the KE family is a
throwback to the chimpanzee version, but that's not the case," says
Fisher. The KEs have the characteristically human form of the gene.
Their mutation affects a part of the FOXP2 protein that interacts
with DNA, which explains why it has trouble orchestrating the
activity of other genes.

There must have been some evolutionary advantage associated with the
human form of FOXP2, otherwise the two mutations would not have
spread so quickly and comprehensively through the population. What
this advantage was, and how it may have related to the rise of
language, is more difficult to say. Nevertheless, clues are starting
to emerge as we get a better picture of what FOXP2 does - not just
in humans but in other animals too.

During development, the gene is expressed in the lungs, oesophagus
and heart, but what interests language researchers is its role in
the brain. Here there is remarkable similarity across species: from
humans to finches to crocodiles, FOXP2 is active in the same
regions. With no shortage of animal models to work with, several
teams have chosen songbirds due to the similarities between their
songs and human language: both build complex sequences from basic
components such as syllables and riffs, and both forms of
vocalisation are learned through imitation and practice during
critical windows of development.

And your bird can sing

All bird species have very similar versions of FOXP2. In the zebra
finch, its protein is 98 per cent identical to ours, differing by
just eight amino acids. It is particularly active in a part of the
basal ganglia dubbed "area X", which is involved in song learning.
Constance Scharff at the Max Planck Institute for Molecular Genetics
in Berlin, Germany, reported that finches' levels of FOXP2
expression in area X are highest during early life, which is when
most of their song learning takes place. In canaries, which learn
songs throughout their lives, levels of the protein shoot up
annually and peak during the late summer months, which happens to be
when they remodel their songs.

So what would happen to a bird's songs if levels of the FOXP2
protein in its area X were to plummet during a crucial learning
window? Scharff found out by injecting young finches with a tailored
piece of RNA that inhibited the expression of the FOXP2 gene. The
birds had difficulties in developing new tunes and their songs
became garbled: they contained the same component "syllables" as the
tunes of their tutors, but with syllables rearranged, left out,
repeated incorrectly or sung at the wrong pitch (PLoS Biology, vol
5, p e321).

The cacophony produced by these finches bears uncanny similarities
to the distorted speech of the afflicted KE family members, making
it tempting to pigeonhole FOXP2 as a vocal learning gene -
influencing the ability to learn new communication sounds by
imitating others. But that is no more accurate than calling it a
"language gene". For a start, songbird FOXP2 has no characteristic
differences to the gene in non-songbirds. What's more, among other
species that show vocal learning, such as whales, dolphins and
elephants, there are no characteristic patterns of mutation in their
FOXP2 that they all share.

Instead, consensus is emerging that FOXP2 probably plays a more
fundamental role in the brain. Its presence in the basal ganglia and
cerebellums of different animals provides a clue as to what that
role might be. Both regions help to produce precise sequences of
muscle movements. Not only that, they are also able to integrate
information coming in from the senses with motor commands sent from
other parts of the brain. Such basic sensory-motor coordination
would be vital for both birdsong and human speech. So could this be
the key to understanding FOXP2?

New work by Fisher and his colleagues supports this idea. Earlier
this year, his team engineered mice to carry the same FOXP2 mutation
that affects the KE family, rendering the protein useless. Mice with
two copies of the dysfunctional FOXP2 had shortened lives,
characterised by motor disorders, growth problems and small
cerebellums. Mice with one normal copy of FOXP2 and one faulty copy
(as is the case in the affected members of the KE family) seemed
outwardly healthy and capable of vocalisation, but had subtle
defects. For example, they found it difficult to acquire new motor
skills such as learning to run faster on a tilted running wheel. An
examination of their brains revealed the problem. The synapses
connecting neurons within the cerebellum, and those in a part of the
basal ganglia called the striatum in particular, were severely
flawed. The signals that crossed these synapses failed to develop
the long-term changes that are crucial for memory and learning
(Current Biology, vol 18, p 354).

"FOXP2 may have some deeply conserved role in neural circuits
involved in learning and producing complex patterns of movement,"
says Fisher. He suspects that mutant versions of FOXP2 disrupt these
circuits and cause different problems in different species. Pääbo
agrees. "Language defects may be where problems with motor
coordination show up most clearly in humans, since articulation is
the most complex set of movements we make in our daily life," he
says. These circuits could underpin the origins of human speech,
creating a biological platform for the evolution of both vocal
learning in animals and spoken language in humans.

The link between FOXP2 and sensory-motor coordination is bolstered
further by research in bats. Sequencing the gene in 13 species of
bats, Shuyi Zhang and colleagues from the East China Normal
University in Shanghai discovered that it shows incredible
diversity. Why would bats have such variable forms of FOXP2 when it
is normally so unwavering in other species? Zhang suspects that the
answer lies in echolocation. He notes that the different versions
seem to correspond with different systems of sonar navigation used
by the various bat species. Although other mammals that use
echolocation, such as whales and dolphins, do not have special
versions of FOXP2, he points out that since they emit their sonar
through their foreheads, these navigation systems have fewer moving
parts. Furthermore, they need far less sensory-motor coordination
than flying bats, which vocalise their ultrasonic pulses and adjust
their flight every few milliseconds, based on their interpretation
of the echoes they receive.

These bats suggest that FOXP2 is no more specific to basic
communication than it is to language, and findings from other
species tell a similar tale. Nevertheless, the discovery that this
is an ancient gene that has assumed a variety of roles does nothing
to diminish the importance of its latest incarnation in humans.
Since its discovery, no other gene has been convincingly implicated
in overt language disorders. FOXP2 remains our only solid lead into
the genetics of language. "It's a molecular window into those kinds
of pathways - but just one of a whole range of different genes that
might be involved," says Fisher. "It's a starting point for us, but
it's not the whole story." He is intent on using FOXP2 to hunt down
other key players in language.

FOXP2 is a transcription factor, which activates some genes while
suppressing others. Identifying its targets, particularly in the
human brain, is the next obvious step. Working with Daniel Geschwind
at the University of California, Los Angeles, Fisher has been trying
to do just that, and their preliminary results indicate just what a
massive job lies ahead. On their first foray alone, the team looked
at about 5000 different genes and found that FOXP2 potentially
regulates hundreds of these. Some of these target genes control
brain development in embryos and its continuing function in adults.
Some affect the structural pattern of the developing brain and the
growth of neurons. Others are involved in chemical signalling and
the long-term changes in neural connections that enable to learning
and adaptive behaviour. Some of the targets are of particular
interest, including 47 genes that are expressed differently in human
and chimpanzee brains, and a slightly overlapping set of 14 targets
that have evolved particularly rapidly in humans. Most intriguingly,
Fisher says, "we think we have evidence that some FOXP2 targets are
also implicated in language impairment." These new results should be
published soon.

Meanwhile, Pääbo has been taking a different approach to finding out
what is special about human FOXP2. His team has engineered mice to
produce a version of the FOXP2 protein with the two
characteristically human mutations. The results are also awaiting
publication but he says that the engineered mice "differ from their
litter-mates in the way they vocalise - although there is no way to
say if they are more human in this respect."

Though talkative mice are likely to remain in the realm of cartoons
for the foreseeable future, the FOXP2 story has already taught us
important lessons about evolution and our place in the natural
world. It shows that our much vaunted linguistic skills are more the
result of genetic redeployment than out-and-out innovation. It seems
that a quest to understand how we stand apart from other animals is
instead leading to a deeper appreciation of what unites us.

Genetics - Keep up with the pace in our continually updated special
report.

The Human Brain - With one hundred billion nerve cells, the
complexity is mind-boggling. Learn more in our cutting edge special
report.

Evolution - Learn more about the struggle to survive in our
comprehensive special report.

Neanderthal echoes

The unique human version of the FOXP2 gives us a surprising link
with one extinct species. Last year, Svante Pääbo's group at the Max
Planck Institute for Evolutionary Anthropology in Leipzig, Germany,
extracted DNA from the bones of two Neanderthals, one of the first
instances of geneticists exploring ancient skeletons for specific
genes. They found that Neanderthal FOXP2 carries the same two
mutations as those carried by us - mutations accrued since our
lineage split from chimps between 6 and 5 million years ago.

Pääbo admits that he "struggled" to interpret the finding: the
Neanderthal DNA suggests that the modern human's version of FOXP2
arose much earlier than previously thought. Comparisons of gene
sequences of modern humans with other living species had put the
origins of human FOXP2 between 200,000 and 100,000 years ago, which
matches archaeological estimates for the emergence of spoken
language. However, Neanderthals split with humans around 400,000
years ago, so the discovery that they share our version of FOXP2
pushes the date of its emergence back at least that far.

"We believe there were two things that happened in the evolution of
human FOXP2," says Pääbo. "The two amino acid changes - which
happened before the Neanderthal-human split - and some other change
which we don't know about that caused the selective sweep more
recently." In other words, the characteristic mutations that we see
in human FOXP2 may indeed be more ancient than expected, but the
mutated gene only became widespread and uniform later in human
history. While many have interpreted Pääbo's findings as evidence
that Neanderthals could talk, he is more cautious. "There's no
reason to assume that they weren't capable of spoken language, but
there must be many other genes involved in speech that we yet don't
know about in Neanderthals."

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Weblinks

Simon Fisher's website
http://www.well.ox.ac.uk/~simon/
Svante Paabo's website
http://www.eva.mpg.de/genetics/files/team_paabo.html
Language Log: blog on the development of language
http://itre.cis.upenn.edu/~myl/languagelog/
Babel's Dawn: blog on the development of language
http://www.ebbolles.typepad.com/

E-mail me if you have problems getting the referenced articles.