cannot be boiled down to one kind of sugar molecule.
We use roughly the same set of genes as other mammals, but we achieve different results with them. How can this be? If two sets of near-identical genes can produce such different-looking animals as a human being and a chimpanzee, then it seems superficially obvious that the source of the difference must lie elsewhere than in the genes. Nurtured as we are in nature–nurture dichotomies, the obvious alternative that occurs to us is nurture. Well, then, do the obvious experiment. Implant a fertilised human egg into the womb of an ape, and vice versa. If nurture is responsible for the difference, the human will give birth to a human and the chimp to a chimp. Any volunteers?
It has been done, though not in apes. In zoos, surrogate mothers have been made to lend their wombs to foetuses from other species in the cause of conservation. The results have been mixed at best. Wild oxen called gaur and banteng have been gestated in cattle, but until now they have died soon after birth. Similar failures have been achieved in wild moufflon gestated in sheep; bongo antelope in eland antelope; Indian desert cat and African wild cat in domestic cats; and Grant’s zebra in domestic horses. The failure of these zoo experiments suggests that a surrogate human mother could not carry a chimpanzee foetus to term. But they do at least prove that in every case, the baby comes out looking like its biological parent, not like its gestational parent. That, indeed, is the point of the experiment: to save rare species by mass-producing them in domestic animals’ wombs.33
It is such an obvious outcome that the experiment seems pointless. We all know that a donkey embryo in a horse womb would develop into a donkey, not a horse. (Donkeys and horses are slightly more similar, genetically, than people and chimps. Like the two ape species, they also differ from each other in that horses have one more pair of chromosomes. This mismatch in chromosome number accounts for the sterility of mules and implies that a man mated to a female chimp just might produce a viable baby who would grow into a sterile ape-person with considerable hybrid vigour. Rumours of Chinese experiments in the 1950s notwithstanding, nobody seems to have tried this simple, but unethical experiment.)
So the conundrum only deepens. The genes, not the womb, determine our species. Yet despite having roughly the same set of genes, human beings and chimpanzees look different. How do you get two different species from one set of genes? How can we have a brain that is three times the size of a chimp’s, and is capable of learning to speak, and yet not have an extra set of genes for making it?
THROWING SWITCHES
I cannot resist a literary analogy. The opening sentence of Charles Dickens’s novel David Copperfield reads: ‘Whether I shall turn out to be the hero of my own life, or whether that station will be held by anybody else, these pages must show.’ The opening sentence of J.D. Salinger’s novel The Catcher in the Rye reads: ‘If you really want to hear about it, the first thing you’ll probably want to know is where I was born, and what my lousy childhood was like, and how my parents were occupied and all before they had me, and all that David Copperfield kind of crap, but I don’t feel like going into it.’ In the pages that follow, to a close approximation, Dickens and Salinger use the same few thousand words. There are words that Salinger uses but not Dickens, like elevator or crap. There are words that Dickens uses but not Salinger, like caul and pettish. But they will be few compared with the words they share. Probably there is at least 90 per cent lexical concordance between the two books. Yet they are very different books. The difference lies not in the use of a different set of words, but in the same set of words used in a different pattern and order. Likewise, the source of the difference between a chimpanzee and a human being lies not in the different genes, but in the same set of 30,000 genes used in a different order and pattern.
I say this with confidence for one main reason. The most stunning surprise to greet scientists when they first lifted the lid on animal genomes was the discovery of the same sets of genes in wildly different animals. In the early 1980s, fly geneticists were thrilled to discover a small group of genes they called the hox genes that seemed to set out the body plan of the fly during its early development – roughly telling it where to put the head, the legs, the wings and so on. But they were completely unprepared for what came next. Their mouse-studying colleagues found recognisably the same hox genes, in the same order, doing the same job. The same gene tells a mouse embryo where (but not how) to grow ribs as tells a fly embryo where to grow wings: you can even swap them between species. Nothing had prepared biologists for this shock. It meant, in effect, that the basic body plan of all animals had been worked out in the genome of a long-extinct ancestor that lived more than 600 million years before and preserved ever since in its descendants (and that includes you).
Hox genes are the recipes for proteins called ‘transcription factors’, which means that their job is to ‘switch on’ other genes. A transcription factor works by attaching itself to a region of DNA called a promoter.34 In creatures such as flies and people (as opposed to bacteria, say), promoters consist of about five separate stretches of DNA code, usually upstream of the gene itself, sometimes downstream. Each of those sequences attracts a different transcription factor, which in turn initiates (or blocks) the transcription of the gene. Most genes will not be activated until several of their promoters have caught transcription factors. Each transcription factor is itself a product of another gene somewhere else in the genome. The function of many genes is therefore to help switch other genes on or off. And the susceptibility of a gene to being switched on or off depends on the sensitivity of its promoters. If its promoters have shifted, or changed sequence so that the transcription factors find them more easily, the gene may be more active. Or if the change has made the promoters attract blocking transcription factors rather than enhancing ones, the gene may be less active.
Small changes in the promoter can therefore have subtle effects on the expression of the gene. Perhaps promoters are more like thermostats than switches. It is here in the promoters that scientists expect to find most evolutionary change in animals and plants – in sharp contrast to bacteria. For example, mice have short necks and long bodies; chickens have long necks and short bodies. If you count the vertebrae in the neck and thorax of a chicken and a mouse, you will find that the mouse has 7 neck and 13 thoracic vertebrae; the chicken has 14 and 7 respectively. The source of this difference lies in one of the promoters attached to one of the hox genes, Hoxc8, a gene found in both mice and chickens whose job is to switch on other genes that lay down details of development. The promoter is a 200-letter paragraph of DNA and it has just a handful of letters different in the two species. Indeed, changes in as few as two of these letters may be enough to make all the difference. The effect is to alter the expression of the Hoxc8 gene slightly in the development of the chicken embryo. In the chicken embryo the gene is expressed in a more limited part of the spine, giving the animal a shorter thorax compared with a mouse.35 In the python, Hoxc8 is expressed right from the head and goes on being expressed for most of the body. So pythons consist of one long thorax – they have ribs all down the body.36
The beauty of the system is that the same gene can be reused in different places and at different times simply by putting a set of different promoters beside it. The ‘eve’ gene in fruit flies, for example, whose job is to switch on other genes during development, is switched on at least ten separate times during the fly’s life, and it has eight separate promoters attached to it, three upstream of the gene and five downstream. Each of these promoters requires 10–15 proteins to attach to it to switch on expression of the eve gene. The promoters cover thousands of letters of DNA text. In different tissues, different promoters are used to switch on the gene. This, incidentally, seems to be one reason for the humiliating fact that plants usually have more genes than animals. Instead of reusing the same gene by adding a new promoter to it, a plant reuses a gene by duplicating the whole gene and changing the promoter in the duplicated version. The 30,000 human genes are probably used in at least twice as many contexts
