of promoters.37
To make grand changes in the body plan of animals, there is no need to invent new genes, just as there is no need to invent new words to write an original novel (unless your name is Joyce). All you need to do is switch the same ones on and off in different patterns. Suddenly, here is a mechanism for creating large and small evolutionary changes from small genetic differences. Merely by adjusting the sequence of a promoter, or adding a new one, you could alter the expression of a gene. And if that gene is itself the code for a transcription factor, then its expression will alter the expression of other genes. Just a tiny change in one promoter will produce a cascade of differences for the organism. These changes might be sufficient to create a wholly new species without changing the genes themselves at all.38
In one sense, this is a bit depressing. It means that until scientists know how to find gene promoters in the vast text of the genome, they will not learn how the recipe of a chimpanzee differs from that of a person. The genes themselves will tell them little, and the source of human uniqueness will remain as mysterious as ever. But in another sense it is also uplifting, reminding us, more forcefully than ever, of a simple truth that is all too often forgotten, that bodies are not made, they grow. The genome is not a blueprint for constructing a body; it is a recipe for baking a body. The chicken embryo is marinaded for a shorter time in the Hoxc8 sauce than the mouse embryo. This is a metaphor I shall return to frequently in the book, for it is one of the best ways of explaining why nature and nurture are not opposed to each other, but work together.
As the hox story illustrates, DNA promoters express themselves in the fourth dimension: their timing is all. A chimp has a different head from a human being not because it has a different blueprint for the head, but because it grows the jaws for longer and the cranium for less long than does the human being. The difference is all timing.
The process of domestication, by which the wolf was turned into the dog, illustrates the role of promoters. In the 1960s, a geneticist named Dmitri Belyaev was running a huge fur farm near Novosibirsk in Siberia. He decided to try to breed tamer foxes, because however well they had been handled and however many generations they had been kept in captivity, foxes were nervous and shy creatures in the fur farm (with good reason, presumably). So Belyaev started by selecting as breeding stock the animals that allowed him closest before fleeing. After 25 generations he did indeed have much tamer foxes, which, far from fleeing, would approach him spontaneously. The new breed of foxes not only behaved like dogs, they looked like dogs: their coats were piebald, like collies, their tails turned up at the end, the females came on heat twice a year, their ears were floppy, their snouts shorter and their brains smaller than in wild foxes. The surprise was that merely by selecting tameness, Belyaev had accidentally achieved all the same features that the original domesticator of the wolf had got – and that was probably some race of the wolf itself, which had bred into itself the ability not to run away too readily from ancient human rubbish dumps when disturbed. The implication is that some promoter change had occurred which affected not one, but many genes. Indeed, it is fairly obvious that what happened in both cases was that the timing of development had been altered so that the adult animals retained many of the features and habits of pups: the floppy ears, the short snout, the smaller skull and the playful behaviour.39
What seems to happen in these cases is that young animals do not yet show either fear or aggression, these developing last during the forward growth of the limbic system at the base of the brain. So the most likely way for evolution to produce a friendly or tame animal is to stop brain development prematurely. The effect is a smaller brain and especially a smaller ‘area 13’, a late-developing part of the limbic system that seems to have the job of disinhibiting adult emotional reactions such as fear and aggression. Intriguingly, such a taming process seems to have happened naturally in bonobos since their separation from the chimpanzee more than two million years ago. For its size the bonobo not only has a small head, but also reduced aggression and several juvenile features retained into adulthood including a white anal tail tuft, high-pitched calls and unusual female genitals. Bonobos have unusually small area 13s.40
So do human beings. Surprisingly, the fossil record suggests that there has been a rather steep decline in human brain size during the past 15,000 years, partly but not wholly reflecting a shrinking body size that seems to have accompanied the arrival of dense and ‘civilised’ human settlement. This followed several million years of more or less steady increases in brain size. In the Mesolithic (around 50,000 years ago) human brains averaged 1,468 cc (in females) and 1,567 cc (in males). Today the numbers have fallen to 1,210 cc and 1,248 cc, and even allowing for some reduction in body weight, this seems to be a steep decline. Perhaps there has been some recent taming of the species. If so, how? Richard Wrangham believes that once human beings became sedentary, living in permanent settlements, they could no longer tolerate anti-social behaviour and they began to banish, imprison or execute especially difficult individuals. In the past in highland New Guinea, more than one in ten of all adult deaths were by the execution of ‘witches’ (mostly men). This might have meant killing the more aggressive and impulsive – hence more developmentally mature and bigger-brained – people.41
Such self-taming, however, seems to be a recent phenomenon in our species and is not able to explain the selective pressures that led to the divergence of human beings from chimp-like ancestors more than five million years ago. But it does support the idea of evolution happening through the adjustment of gene promoters rather than genes themselves: hence the alteration of several irrelevant features caught in the slipstream of a reduction in impulsive aggression.42 Meanwhile, it is suddenly looking possible to understand how the human brain achieved its enlarged size in the first place, thanks to a newly discovered gene on chromosome 1. Following the completion of a dam in Mirpur, in Pakistani-controlled Kashmir in 1967, a large number of local people, displaced from their homes, migrated to Bradford in England. They included some who had married cousins, and among the offspring of these cousin marriages were a few people born with abnormally small, though otherwise normal brains – so-called microcephalics. The family pedigrees allowed scientists to pin down the cause as four different mutations in different families, but all affecting the same gene: the ASPM gene on chromosome 1.
On further investigation, a team of scientists led by Geoffrey Woods in Leeds discovered something rather extraordinary about the gene. It is a large gene, 10,434 letters long and split into 28 paragraphs (called exons). The 16th to 25th paragraphs contain a characteristic motif repeated over and over again. The phrase, usually 75 letters long, begins with the code for the amino acids isoleucine and glutamine, the significance of which I will reveal in a moment. In the human version of the gene, there are 74 such motifs, in the mouse 61, in the fruit fly 24 and in the nematode worm just 2 repetitions. Remarkably, these numbers seem to be in proportion to the number of neurons in the adult brain of the animal.43 Even more remarkably, the standard abbreviation for isoleucine is ‘I’ and the abbreviation for glutamine is ‘Q’. Therefore, the number of IQ repeats may determine the relative IQ of the species, which, according to Woods, ‘is a proof of God’s existence since only someone with a sense of humour could have arranged for the correlation’.44
ASPM seems to work by regulating the number of times neuronal stem cells divide inside the vesicles of the young brain about two weeks after conception. This in turn decides how many neurons the adult brain will have. To have stumbled on a gene with the power to decide brain size in such a simple manner seems almost too good to be true, and complications will undoubtedly crowd in upon this simple story as more comes to be known. But the ASPM gene vindicates that young man who was so startled by the Fuegians: evolution is a difference of degree, not kind.
The
