A different version of this story appears at The Scientist.
Honeybee workers spend their whole lives toiling for their hives, never ascending to the royal status of queens. But they can change careers. At first, they’re nurses, which stay in the hive and tend to their larval sisters. Later on, they transform into foragers, which venture into the outside world in search of flowers and food.
This isn’t just a case of flipping between tasks. Nurses and foragers are very distinct sub-castes that differ in their bodies, mental abilities, and behaviour – foragers, for example, are the ones that use the famous waggle dance. “[They’re] as different as being a scientist or journalist,” explains Gro Amdam, who studies bee behaviour. “It’s really amazing that they can sculpt themselves into those two roles that require very specialist skills.” The transformation between nurse and forager is significant, but it’s also reversible. If nurses go missing, foragers can revert back to their former selves to fill the employment gap.
Amdam likens them to the classic optical illusion (shown on the right) which depicts both a young debutante and an old crone. “The bee genome is like this drawing,” she says. “It has both ladies in it. How is the genome able to make one of them stand out and then the other?
The answer lies in ‘epigenetic’ changes that alter how some of the bees’ genes are used, without changing the underlying DNA. Amdam and her colleague Andrew Feinberg found that the shift from nurse to forager involves a set of chemical marks, added to the DNA of few dozen genes. These marks, known as methyl groups, are like Post-It notes that dictate how a piece of text should be read, without altering the actual words. And if the foragers change back into nurses, the methylation marks also revert.
Together, they form a toolkit for flexibility, a way of seeing both the crone and the debutante in the same picture, a way of eking out two very different and reversible skill-sets from the same genome.
Writers often compare the human genome to a collection of recipes for making a person. Each gene contains the instructions for building a protein, and our thousands of proteins work together to build and maintain our bodies.
But if the genome is a recipe book, it’s one that was written without a good editor. It is riddled with typos, unnecessary repetitions and meaningless drivel. A miniscule proportion actually codes for proteins. The rest looks like a scrapyard. It contains the remnants of dead genes that are no longer used and have degenerated into nonsense. It contains jumping genes that hop around the genome under their own power, sometimes leaving copies of themselves behind. And it contains the remains of these jumping genes, which have lost their hopping ability and stayed in place.
These “non-coding sequences” are often called junk DNA, and for good reason. It seems that they’re largely useless… but not entirely so. Ever since these non-coding sequences were first discussed, scientists have suspected that some of them play fruitful roles in the body. Many examples have since come to light, and Francois Cartault and his colleagues have found the latest one. He has shown that one piece of supposed “junk” might explain why some people from a tiny French island die from a bizarre brain disease.
Update: I’ve amended this post following some harsh critical comments on the study from geneticists on Twitter, which I really should have noted while going through the paper.
Our genes can influence our behaviour in delicate ways, and these effects, while subtle, are not undetectable. Scientists can pick them up by studying large groups of people, but individuals can sometimes be sensitive to these small differences.
Consider the OXTR gene. It creates a docking station for a hormone called oxytocin, which has far-ranging effects on our social behaviour. People carry either the A or G versions of OXTR, depending on the “letter” that appears at a particular spot along its length. People with two G-copies tend to be more empathic, sociable and sensitive than those with at least one A-copy. These differences are small, but according to a new study from Aleksandr Kogan at the University of Toronto, strangers can pick up on them after watching people for just a few minutes.
If you watch chimpanzees from different parts of Africa, you’ll see them doing very different things. Some use sticks to extract honey from beehives, while others prefer leaves. Some use sticks as hunting spears and others use them to fish for ants. Some drum on branches to get attention and others rip leaves between their teeth.
These behaviours have been described as cultural traditions; they’re the chimp equivalent of the musical styles, fashion trends and social rules of humans. They stem from the readiness of great apes to ape one another and pick up behaviours from their peers. But a new study complicates our understanding of chimp cultures. Kevin Langergraber at the Max Planck Institute for Evolutionary Anthropology has found that much of this variation in behaviour could have a genetic influence.
There are great plays and bad ones, but the playwright’s actual text is only one aspect of a production. The very same words can take on radically different meanings depending on the whims of the director, the abilities of the actors and the setting of the stage. The same is true of our genes and our environments. In cases where genes affect our behaviour, the same stretch of DNA can lead to very different deeds, depending on individual circumstances. Just as a production defines a play, environments and cultures alter the effects of certain genes.
Heejung Kim from the University of California has discovered a great example of this effect by studying a gene called OXTR (or the ‘oxytocin receptor’, in full). The gene creates a docking station for a hormone called oxytocin, which is involved in all sorts of emotions and social behaviours, from trust to sexual arousal to empathy.
Kim looked at a specific version of the OXTR gene, whose carriers are allegedly more social and sensitive. But this link between gene and behaviour depends on culture; it exists among American people, who tend to look for support in troubled times, but not in Korean cultures, where such support is less socially acceptable. Culture sets the stage on which the OXTR gene expresses itself. Read More
Genetic studies suggest that genes have a big influence on a child’s reading ability. Twins, for example, tend to share similar reading skills regardless of whether they share the same teacher. On the other hand, other studies have found that the quality of teaching that a child receives also has a big impact on their fluency with the written word. How can we make sense of these apparently conflicting results? Which is more important for a child’s ability to read: the genes they inherit from their parents, or the quality of the teaching they receive?
According to a new study, the answer, perhaps unsurprisingly, is both. Genes do have a strong effect on a child’s reading ability, but good teaching is vital for helping them to realise that potential. In classes with poor teachers, all the kids suffer regardless of the innate abilities bestowed by their genes. In classes with excellent teachers, the true variation between the children becomes clearer and their genetic differences come to the fore. Only with good teaching do children with the greatest natural abilities reach their true potential.
This study demonstrates yet again how tired the “nature versus nurture” debate is. As I wrote about recently in New Scientist, nature and nurture are not conflicting forces, but partners that work together to influence our behaviour.
This latest choreography of genes and environment was decoded by Jeanette Taylor from Florida State University. She studied over 800 pairs of Florida twins in the first and second grades. Of the pairs, 280 are identical twins who share 100% of their DNA, and 526 are non-identical twins who share just 50% of their DNA. These twin studies are commonly used to understand the genetic influences of behaviour. If a trait is strongly affected by genes, then the variation in that trait should be less pronounced in the identical twins than the non-identical ones.
I’ve got a feature in the latest issue of New Scientist. It’s sort of a four-step guide to interpreting studies looking at genes and behaviour, using one particular gene as a case study. The piece is out today, but it harkens back to lines of thinking that began over a century ago.
Italy, 1876. The criminologist and physician Cesare Lombroso has just published L’uomo delinquente (The Criminal Man), a work that will define European understanding of criminal behaviour for several decades. Lombroso believed that some people were born criminals, whose penchant for crime was set from birth and who had diminished responsibility for their own misdeeds.
Skip forward 133 years, and Lombroso’s theories seem antiquated, even distasteful. Our modern understanding of biology has put paid to simplistic ideas about the origins of criminality and violence. Discoveries from the growing field of ‘behavioural genetics’ show us how nature and nurture conspire to influence our actions. But because of these same discoveries, the idea of the born criminal has resurfaced in modern Italy under a different guise, a century after Lombroso’s death.
Last year, Italian courts cut the sentence of a convicted murderer by one year, on the basis that his genetic make-up supposedly predisposed him to violence. The man, Abdelmalek Bayout, carried a version of a gene called monoamine oxidase A, or MAOA, which has been linked to aggression and violence. The gene has a history of controversy. It has been linked to gang membership and psychological disorders, and it has been used to define an entire ethnic group as warriors.
The story of MAOA is the perfect case study for how gradual revelations about the tango between genes and environment can be translated into unconvincing applications and overplayed interpretations. There is no better example of the dangerous state of modern behavioural genetics, no better poster child for how to miscommunicate, misinterpret and misuse genetic discoveries.
The feature takes the form of four lessons, each covering a different area of research or controversy around MAOA:
Today, a new paper published in Nature adds another chapter to the story of FOXP2, a gene with important roles in speech and language. The FOXP2 story is a fascinating tale that I covered in New Scientist last year. It’s one of the pieces I’m proudest of so I’m reprinting it here with kind permission from Roger Highfield, and with edits incorporating new discoveries since the time of writing.
The FOXP2 Story (2009 edition)
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.”
Two amino acids, two hundred thousand years
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.
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 below).
“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.
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.
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. In 2008, 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. The opposite happened when the team engineered mice to produce a version of FOXP2 with the two characteristically human mutations. Their basal ganglia had neurons with longer outgrowths (dendrites) that were better able to strengthen or weaken the connections between them.
A battery of over 300 physical and mental tests showed that the altered mice were generally healthy. While they couldn’t speak like their cartoon equals, their central nervous system developed in different ways, and they showed changes in parts of the brain where FOXP2 is usually expressed (switched on) in humans.
Their squeaks were also subtly transformed. When mouse babies are moved away from their nest, they make ultrasonic distress calls that are too high for us to hear, but that their mothers pick up loudly and clearly. The altered Foxp2 gene subtly changed the structure of these alarm calls. We won’t know what this means until we get a better understanding of the similarities between mouse calls and human speech.
For now, the two groups of engineered mice tentatively support the idea that human-specific changes to FOXP2 affect aspects of speech, and strongly support the idea that they affect aspects of learning. “This shows, for the first time, that the [human-specific] amino-acid changes do indeed have functional effects, and that they are particularly relevant to the brain,” explains Fisher. “FOXP2 may have some deeply conserved role in neural circuits involved in learning and producing complex patterns of movement.” 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.
Holy diversity, Batman
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 has already used FOXP2 to hunt down other key players in language.
The executive’s minions
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 have evidence that some FOXP2 targets are also implicated in language impairment.” Last year, Sonja Vernes in his group showed that FOXP2 switches off CNTNAP2, a gene involved in not one but two language disorders – specific language impairment (SLI) and autism. Both affect children, and both involve difficulties in picking up spoken language skills. The protein encoded by CNTNAP2 is deployed by nerve cells in the developing brain. It affects the connections between these cells and is particularly abundant in neural circuits that are involved in language.
Verne’s discovery is a sign that the true promise of FOXP2’s discovery is being fulfilled – the gene itself has been overly hyped, but its true worth lies in opening a door for more research into genes involved in language. It was the valuable clue that threw the case wide open. CNTNAP2 may be the first language disorder culprit revealed through FOXP2 and it’s unlikely to be the last.
Most recently, Dan Geschwind compared the network of genes that are targeted by FOXP2 in both chimps and humans. He found that the two human-specific amino acids within this executive protein have radically altered the set of genetic minions that it controls.
The genes that are directed by human FOXP2 are a varied cast of players that influence the development of the head and face, parts of the brain involved in motor skills, the growth of cartilage and connective tissues, and the development of the nervous system. All those roles fit with the idea that our version of FOXP2 has been a lynchpin in evolving the neural circuits and physical structures that are important for speech and language.
The FOXP2 story is far from complete, and every new discovery raises fresh questions just as it answers old ones. Already, this gene 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.
Box – 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.”
This article is reposted from the old WordPress incarnation of Not Exactly Rocket Science. The blog is on holiday until the start of October, when I’ll return with fresh material.
As a species, we value fair play. We’re like it so much that we’re willing to eschew material gains in order to punish cheaters who behave unjustly. Psychological games have set these maxims in stone, but new research shows us that this sense of justice is, to a large extent, influenced by our genes.
When it comes to demonstating our innate preference for fair play, psychologists turn to the ‘Ultimatum Game‘, where two players bargain over a pot of money. The ‘proposer’ suggests how the money should be divided and the ‘receiver’ can accept of refuse the deal. If they refuse, neither player gets anything and there is no room for negotiation. In a completely rational setting, the proposer should offer the receiver as little as possible, and the receiver should take it – after all, a very little money is better than none at all.
Of course, that’s not what happens. Receivers typically abhor unfair offers and would rather that both parties receive no money than accept a patronisingly tiny amount. Across most Western countries, proposers usually offer the receivers something between 40% and 50% of the takings. Any offers under 10% are almost always rejected.
The uniformity of responses across Western countries suggests that culture has a strong effect on how people play the game, but until now, no one had looked to see how strongly genes asserted their influence. Bjorn Wallace and colleagues from the Stockholm School of Economics decided to do just that, and they used the classic experiment for working out heritability – the twin study.
The trauma of child abuse can last a lifetime, leading to a higher risk of anxiety, depression and suicide further down the line. This link seems obvious, but a group of Canadian scientists have found that it has a genetic basis.
By studying the brains of suicide victims, Patrick McGowan from the Douglas Mental Health University Institute, found that child abuse modifies a gene called NR3C1 that affects a person’s ability to deal with stress. The changes it wrought were “epigenetic”, meaning that the gene’s DNA sequence wasn’t altered but it’s structure was modified to make it less active. These types of changes are very long-lasting, which strongly suggests that the trauma of child abuse could be permanently inscribed onto a person’s genes.
Child abuse, from neglect to physical abuse, affects the workings of an important group of organs called the “hypothalamic-pituitary-adrenal axis” or HPA. This trinity consists of the hypothalamus, a funnel-shaped part of the brain; the pituitary gland, which sits beneath it; and the adrenal glands, which sit above the kidneys. All three organs secrete hormones. Through these chemicals, the HPA axis controls our reactions to stressful situations, triggering a number of physiological changes that prime our bodies for action.
The NR3C1 gene is part of this system. It produces a protein called the glucocorticoid receptor, which sticks to cortisol, the so-called “stress hormone”. Cortisol is produced by the adrenal glands in response to stress, and when it latches on to its receptor, it triggers a chain reaction that deactivates the HPA axis. In this way, our body automatically limits its own response to stressful situations.
Without enough glucocorticoid receptors, this self-control goes awry, which means that the HPA is active in normal situations, as well as stressful ones. No surprise then, that some scientists have found a link between low levels of this receptor and schizophrenia, mood disorders and suicide. So, childhood trauma alters the way the body reacts to stress, which affects a person’s risk of suicide or mental disorders later in life. Now, McGowan’s group have revealed part of the genetic (well, epigenetic) basis behind this link.