Men who think that size really matters should probably not think too hard about the Y chromosome. This bundle of genes is the ultimate determinant of manliness, and it happens to be a degenerate runt. Over a few hundred million years, it has shrunk considerably, jettisoning around 97% of its original genes. Where it was once a large library of genes, now it’s more a struggling independent bookstore. This loss of information defined the youth of the Y chromosome but nowadays, things are different. Renovation is the order of the day.
Jennifer Hughes from MIT revealed the recent history of the Y chromosome by comparing the human and chimp versions. They are incredibly different. They have rapidly evolved since the two species last shared a common ancestor 6 million years ago. In this relatively short span of time, the two Ys have accumulated differences that other chromosomes would take 310 million years to build up. It’s the sort of genetic disparity you’d expect to see between humans and chickens, not between us and our closest relatives!
This drastic remodelling contradicts the current view of Y evolution, which suggests that the chromosome has stagnated. It has lost so many of its genes that some scientists thought it might waste away altogether within another 10 million years. But rumours of its impending demise had been greatly exaggerated. In 2005, Hughes showed that Y isn’t shrinking at the breakneck pace of old.
That result was based on a comparison of individual genes on the two chromosomes. Since then, Hughes has managed to fully sequence the chimp Y, the first time this has been accomplished for a non-human animal. Considering how small the chromosome is, sequencing it is remarkably tricky. It has lots of long, repetitive sequences that are subtly different and hard to tell apart through conventional means.
Nonetheless, Hughes managed it. By comparing the two sequences, she found that the Y chromosome is an island of difference in a sea of resemblance. The chimp and human genomes are famous for their similarity; they’re a 98.8% match for each other. And indeed, where the chimp and human Y sequences align, they are a 98% match, just like the rest of the genome. But they don’t align very well. Around 30% of the chimp Y chromosome has no human counterpart and vice versa.
At first glance, the African elephant doesn’t look like it has much in common with us humans. We support around 70-80 kg of weight on two legs, while it carries around four to six tonnes on four. We grasp objects with opposable thumbs, while it uses its trunk. We need axes and chainsaws to knock down a tree, but it can just use its head. Yet among these differences, there is common ground. We’re both long-lived animals with rich social lives. And we have very, very large brains (well, mostly).
But all that intelligence doesn’t come cheaply. Large brains are gas-guzzling organs and they need a lot of energy. Faced with similarly pressing fuel demands, humans and elephants have developed similar adaptations in a set of genes used in our mitochondria – small power plants that supply energy to our cells. The genes in question are “aerobic energy metabolism (AEM)” genes – they govern how the mitochondria metabolise nutrients in food, in the presence of oxygen.
We already knew that the evolution of AEM genes has accelerated greatly since our ancestors split away from those of other monkeys and apes. While other mutations were reshaping our brain and nervous system, these altered AEM genes helped to provide our growing cortex with much-needed energy.
Now, Morris Goodman from Wayne State University has found evidence that the same thing happened in the evolution of modern elephants. It’s a good thing too – our brain accounts for a fifth of our total demand for oxygen but the elephant’s brain is even more demanding. It’s the largest of any land mammal, it’s four times the size of our own and it requires four times as much oxygen.
Goodman was only recently furnished with the tools that made his discovery possible – the full genome sequences of a number of oddball mammals, including the lesser hedgehog tenrec (Echinops telfairi). As its name suggests, the tenrec looks like a hedgehog, but it’s actually more closely related to elephants. Both species belong to a major group of mammals called the afrotherians, which also include aardvarks and manatees.
Goodman compared the genomes of 15 species including humans, elephants, tenrecs and eight other mammals and looked for genetic signatures of adaptive evolution. The genetic code is such as that a gene can accumulate many changes that don’t actually affect the structure of the protein it encodes. These are called “synonymous mutations” and they are effectively silent. Some genetic changes do, however, alter protein structure and these “non-synonymous mutations” are more significant and more dramatic, for even small tweaks to a protein’s shape can greatly alter its effectiveness. A high ratio of non-synonymous mutations compared to synonymous ones is a telltale sign that a gene has been the target of natural selection.
And sure enough, elephants have more than twice as many genes with high ratios of non-synonymous mutations to synonymous ones than tenrecs do, particularly among the AEM genes used in the mitochondria. In the same way, humans have more of such genes compared to mice (which are as closely related to us, as tenrecs are to elephants).
These changes have taken place against a background of less mutation, not more. Our lineage, and that of elephants, has seen slower rates of evolution among protein-coding genes, probably due to the fact that the duration of our lives and generations have increased. Goodman speculates that with lower mutation rates, we’d be less prone to developing costly faults in our DNA every time it was copied anew.
Overall, his conclusion was clear – in the animals with larger brains, a suite of AEM genes had gone through an accelerated burst of evolution compared to our mini-brained cousins. Six of our AEM genes that appear to have been strongly shaped by natural selection even have elephant counterparts that have gone through the same process.
Of course, humans and elephants are much larger than mice and tenrecs. But our genetic legacy isn’t just a reflection of our bigger size, for Goodman confirmed that AEM genes hadn’t gone through a similar evolutionary spurt in animals like cows and dogs.
Goodman’s next challenge is to see what difference the substituted amino acids would have made to us and elephants and whether they make our brains more efficient at producing aerobic energy. He also wants to better understand the specific genes that have been shaped the convergent evolution of human and elephant brains over the course of evolution. That task should certainly become easier as more and more mammal genomes are published.
Reference: PNAS doi:10.1073/pnas.0911239106
More on elephants:
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.”
From a young age, children learn about the sounds that animals make. But even without teaching aides like Old Macdonald’s farm, it turns out that very young babies have an intuitive understanding of the noises that humans, and even monkeys, ought to make. Athena Vouloumanos from New York University found that at just five months of age, infants match human speech to human faces and monkey calls to monkey faces. Amazingly, this wasn’t a question of experience – the same infants failed to match quacks to duck faces, even though they had more experience with ducks than monkeys.
Voloumanos worked with a dozen five-month-old infants from English- and French-speaking homes. She found that they spent longer looking at human faces when they were paired with spoken words than with monkey or duck calls. They clearly expect human faces, and not animal ones, to produce speech, even when the words in question came from a language – Japanese – that they were unfamiliar with. However, the fact that it was speech was essential; human laughter failed to grab their attention in the same way, and they didn’t show any biases towards either human or monkey faces.
More surprisingly, the babies also understood the types of calls that monkeys ought to make. They spent more time staring at monkey faces that were paired with monkey calls, than those paired with human words or with duck quacks.
That’s certainly unexpected. These babies had no experience with the sight or sounds of rhesus monkeys but they ‘got’ that monkey calls most likely come from monkey faces. Similarly, they appreciated that a human face is an unlikely source of a monkey call even though they could hardly have experienced every possible sound that the human mouth can make.
Perhaps they were just lumping all non-human calls and faces into one category? That can’t be true, for they would have matched the monkey faces to either monkey or duck calls. Perhaps they matched monkeys to their calls because they ruled out a link to more familiar human or duck sounds? That’s unlikely too, for the infants failed to match ducks faces to quacks!
Instead, Vouloumanos believes that babies have an innate ability to predict the types of noises that come from certain faces, and vice versa. Anatomy shapes the sound of a call into a audio signature that’s specific to each species. A human vocal tract can’t produce the same repertoire of noises as a monkey’s and vice versa. Monkeys can produce a wider range of frequencies than humans can, but thanks to innovations in the shape of our mouth and tongue, we’re better at subtly altering the sounds we make within our narrower range.
So the very shape of the face can provide clues about the noises likely to emerge from it, and previous studies have found that infants are very sensitive to these cues. This may also explain why they failed to match duck faces with their quacks – their visages as so vastly different to the basic primate design that they might not even be registered as faces, let alone as potential clues about sound.
If that’s not enough, Vouloumanos has a second possible explanation – perhaps babies use their knowledge of human sounds to set up a sort of “similarity gradient”. Simply put, monkey faces are sort of like human faces but noticeably different, so monkey calls should be sort of like human calls but noticeably different.
Either way, it’s clear that very young babies are remarkably sensitive to the sounds of their own species, particularly those of speech. The five month mark seems to be an important turning point, not just for this ability but for many others. By five months, they can already match faces with voices on the basis of age or emotion, but only after that does their ear for voices truly develop, allowing them to tune in to specific voices, or to the distinct sounds of their native language.
Reference: PNAS doi: 10.1073/pnas.0906049106
More on child development:
For all appearances, this looks like the skull of any human child. But there are two very special things about it. The first is that its owner was clearly deformed; its asymmetrical skull is a sign of a medical condition called craniosynostosis
that’s associated with mental retardation. The second is that the skull is about half a million years old. It belonged to a child who lived in the Middle Pleistocene period.
The skull was uncovered in Atapuerca, Spain by Ana Gracia, who has named it Cranium 14. It’s a small specimen but it contains enough evidence to suggest that the deformity was present from birth and that the child was about 5-8 years old. The remains of 28 other humans have been recovered from the same site and none of them had any signs of deformity.
These facts strongly suggest that prehistoric humans cared for children with physical and mental deformities that would almost have certainly prevented them from caring for themselves. Without such assistance, it’s unlikely that the child would have survived that long.
Be it in sports or comedy, they say that timing is everything. In evolution, it’s no different. Many of the innovations that have separated us from other apes may have arisen not through creating new genetic material, but by subtly shifting how the existing lot is used.
Take our brains, for example. In the brains of humans, chimps and many other mammals, the genes that are switched on in the brain change dramatically in the first few years of life. But Mehmet Somel from the Max Planck Institute for Evolutionary Anthropology has found that a small but select squad of genes, involved in the development of nerve cells, are activated much later in our brains than in those of other primates.
This genetic delay mirrors other physical shifts in timing that separate humans from other apes. Chimpanzees, for example, become sexually mature by the age of 8 or 9; we take five more years to reach the same point of development.
These delays are signs of an evolutionary process called “neoteny“, where a species’ growth slows down to the point where adults retain many of the features previously seen juveniles. You can see neoteny at work in some domestic dog breeds, which are remarkably similar to baby wolves, or the axolotl salamander, which keeps the gills of a larva even as it becomes a sexually mature adult. And some scientists, like the late Stephen Jay Gould, have suggested that neoteny has played a major role in human evolution too.
As adults, we share many of the physical features of immature chimps. Our bone structures, including flat faces and small jaws, are similar to those of juvenile chimps, as is our patchy distribution of hair. A slower rate of development may even have shaped our vaunted intelligence, by stretching out the time when we are most receptive to new skills and knowledge. Somel’s research supports this idea by showing that since our evolutionary split from chimpanzees, the activation of some important brain genes has been delayed to the very start of adolescence.