smrize logo

Want to extract relevant stories from a book? - Drop us a line at feedback@smrize.com

Book Summary: The Book of Humans: A Brief History of Culture, Sex, War and the Evolution of Us

Author: Adam Rutherford

Substory: Trippingly on the Tongue

There is one gene that is worth scrutinising in much more depth. It’s a gene that has much to say about our history and speaks volumes about evolution, and how we talk about evolution, and that is because it is a gene essential for speech. The story begins in Great Ormond Street Hospital in London in the 1990s. A family, known simply as KE, were being treated for a particular type of rare verbal apraxia, meaning that many members of the family had significant difficulty in turning sounds into syllables, syllables into words, and words into sentences. Fifteen people across three generations had these symptoms, most obviously the children, who would say things like ‘bu’ instead of ‘blue’, and ‘boon’ instead of ‘spoon’, among other verbal flubs. Further investigation showed that affected members of the family also had troubles that were not just related to articulation of words, but with more basic but specific movements of the face and mouth. When the same condition is seen in multiple generations in one family, we draw a pedigree and label the members who bear it. We can therefore assume that the random shuffling of genomes that happens when sperm and egg are made has not diluted the disease-causing DNA out of the lineage, but has been retained in those individuals. The inheritance pattern in the KE family pointed towards a single genetic defect being the cause. Though things are hugely more complicated now, at that time in the history of clinical genetics, most of the diseases that had been identified were indeed rooted in a single gene – conditions such as cystic fibrosis, Huntingdon’s disease or haemophilia. In those ancient days of genetics, researchers would use a pedigree like this to hunt down a gene, and in 1998 Simon Fisher and his team found the sole cause of this family’s speech and language problems. It was a gene that was named FOXP2, and since then has become an icon in genetics and evolution.

The gene FOXP2 encodes a transcription factor.1 These are proteins whose only function is to clamp onto very specific bits of DNA (such as the enhancer HACNS1 described above). That way, one gene can control the activity of a second, a third, and so on, and a cascade of complex activity is triggered that helps to specify the different cells and tissue in a developing embryo. All genes are important, but some are more important than others, and transcription factors fall into that latter category. During your time as an embryo in utero, you grew from one single cell into trillions, carefully arranged into different types of cell, in different tissues doing very specific things. Transcription factors have a major role in the growth of an embryo. They function as controllers, busying away like foremen, setting up major building works, such as determining which end of an amorphous blob of cells is going to be the head and which the tail. Once that is in place, other transcription factors can set up ever-more precise plans that specify ‘a brain goes up at this end’, ‘in the brain area, eyes go here’, ‘in the eye area, the retina goes here’, ‘in the retina, the photoreceptors go here’ and ‘among photoreceptors, these ones are going to be rods’. The details get more and more specific as the embryo develops, and the tissues differentiate into their mature fates. FOXP2 is one of those which operates in the middle of those grand schemes of a developing embryo, and primarily has the effect of instructing the growth of more cells. When we look at where it is active in an embryo, it’s in discrete areas all over the brain, clearly directing all sorts of neuronal growth, including in motor circuitry, the basal ganglia, thalamus and cerebellum.

Of the weapons in the arsenal of geneticists, seeing where the gene is active is just one. We can also extract the protein and see what it interacts with, a sort of molecular fishing trip. When we fish with FOXP2, it is fairly promiscuous, but some of its targets again offer alluring clues, such as a short stretch of DNA known as CNTNAP2, which is itself associated with speech disorders.

With all this in place, we have a gene that, when defective, causes a litany of speech and language disorders, and is active in various bits of tissue that are closely associated with speech. Other animals communicate orally, but in terms of sophistication, our language trumps even the closest by miles by every measure.2 Given that we are the only organism that speaks with complex syntax and grammar, a genetic basis for our language skills is of great use in trying to demarcate ourselves as different from the other animals.

FOXP2 was not created de novo in us. In fact, it is an extremely ancient gene, as transcription factors often are. Similar versions are found in mammals, reptiles, fish and birds, many of which vocalise in some form. We know that in songbirds, their version of FOXP2 is active in the brain when they are learning new songs from other males to woo females.

In chimpanzees, their FOXP2 is only two amino acids different out of the 700 that make up the protein, but the consequences are clearly significant – we speak and they do not. In Neanderthals, it is the same as in us, but other sections of their DNA may regulate differences in what the gene is doing. In mice, with whom we last shared a common ancestor about nine million years before the dinosaurs were wiped out, they have a version of FOXP2 that is only four amino acids different. When we look at where the mouse Foxp2 is active, it’s in entirely equivalent places in the brain during development. When one copy of the gene is experimentally removed in mice, they display some abnormalities, one of which is a reduction in the number of ultrasonic peeps that pups usually make (if both copies are knocked out, the baby mice die after twenty-one days).

The fact that it is clearly essential for human speech and grammar, that it is different in us from the mice and chimp versions, and that it has undergone positive selection in Homo sapiens shows the elemental importance of FOXP2. It shows that this one particular gene is terribly important, but not all-important.