The Language of the Genes. Steve Jones
claim: that while only a few preserve their heritage in an ostentatious way, every family, aristocratic or not, retains the record of their ancestors. Everyone, however deficient in history, can decipher their past in the narrative of the DNA.
Some can use inherited abnormalities. A form of juvenile blindness called hereditary glaucoma is found in France. Parish records show that most cases descend from a couple who lived in the village of Wierr-Effroy near Calais in the fifteenth century. Even today pilgrims pray in the village church of Sainte Godeleine, which contains a cistern whose waters are believed to cure blindness. Thirty thousand descendants have been traced and for many the diagnosis of the disease was their first clue about where their ancestors came from and who their relatives might be. The gene went with French emigrants to the New World.
Human genetics was, until recently, restricted to studying pedigrees that stood out because they contained an inborn disease. Its ability to trace descent was limited to those few kindreds who appear to deviate from some perfect form. Biology has now shown that perfection is a mirage and that, instead, variation rules. Thousands of characters – normal diversity, not diseases – distinguish each nation, each family and each person. Everyone alive today is different from everyone who ever has lived or ever will live. Such variation can be used to look at shared ancestry in any lineage, healthy or ill, aristocratic or plebeian. Every modern gene brings clues from parents and grandparents, from the earliest humans a hundred thousand years and more ago and from the origin of life four thousand million years before that.
Most of genetics is no more than a search for diversity. Some differences can be seen with the naked eye. Others need the most sophisticated methods of molecular biology. As a sample of how different each individual is we can glance beneath the way we look to ask about variation in how we sense the world and how the world perceives us.
Obviously, people do not much resemble each other. The inheritance of appearance is not simple. Eye colour depends first on whether any pigment is present. If none is made the eye is pale blue. Other tints vary in the amounts of the pigment made by several distinct genes, so that colour is not a dependable way of working out who fathered a particular child. The inheritance of hair type is also rather complex. Apart from very blonde or very red hair, the genetics of the rest of the range is confused and is further complicated by the effects of age and exposure to the sun.
Even a trivial test shows that individuals differ in other ways. Stick your tongue out. Can you roll it into a tube? About half those of European descent can and half cannot. Clasp your hands together. Which thumb is on top? Again, about half the population folds the left thumb above the right and about half do it the other way. These attributes run in families but their inheritance, like that of physical appearance, is uncertain.
People vary not just in the way the world sees them, but how they see it. A few are colour-blind. They lack a receptor for red, green or blue light. All three are needed to perceive the full range of colour. The absence of (or damage to) one (usually that for green, less often for red, almost never for blue) gives rise to a mild disability that may have made a difference when gathering food in ancient times. The three genes involved have now been tracked down. Those for red and green are similar and diverged not long ago, while the blue receptor has an identity of its own. John Dalton, best known for his atomic theory, was himself so colour-blind as to match red sealing-wax with a leaf (which must have made things difficult for a chemist). He believed that his own eyes were tinted with a blue filter and asked that they be examined after his death. They were, and no filter was found, but, a century and a half later, a check of the DNA in his pickled eyeballs showed him to have lacked the green-sensitive pigment.
Colour-blindness marks the extreme of a system of normal variation in perception. When asked to mix red and green light until they match a standard orange colour, people divide into two groups that differ in the hue of the red light chosen. There are two distinct receptors for red, differing in a single change in the DNA. About sixty per cent of Europeans have one form, forty per cent the other. Both groups are normal (in the sense that they are aware of no handicap) but one sees the world through rather more rose-tinted spectacles than the other. The contrast is small but noticeable. If two men with different red receptors were to choose jacket and trousers for Father Christmas there would be a perceptible clash between upper and lower halves.
In the 1930s, a manufacturer of ice trays was surprised to receive complaints that his trays made ice taste bitter. This baffled the entrepreneur as the ice tasted just like ice to him, but was a hint of inherited differences in the ability to taste. To some, a trace of a substance used in the manufacturing process is intolerable, while to others a concentration a thousand times greater has no taste at all. Much of the difference depends on just one gene which exists in two forms. That observation, the ability or otherwise to perceive a substance, now called PROP, was the key to a new universe of taste. Genetic ‘supertasters’ are very sensitive to the hops in beer, to pungent vegetables like broccoli, to sugar and to spices, while non-tasters scarcely notice them. Half the population of India cannot taste the chemical at all, but just one African in thirty is unable to perceive it. Students of my day thought it witty to make tea containing PROP to see the bafflement of those who could drink it and those who could not. Today’s undergraduates have more sense.
As truffle-hunters know, scent and taste are related. There is genetic variation in the ability to smell, among other things, sweat, musk, hydrogen cyanide and the odour of freesias. Many animals communicate with each other through the nose. Female mice can smell not only who a male is, but how close a relative he might be. Humans also have an odorous identity, as police dogs find it more difficult to separate the trails of identical twins (who have all their genes in common) than those of unrelated people. Man has more scent glands than does any other primate, perhaps as a remnant of some uniqueness in smell which has lost its importance in a world full of sight. The tie between sex and scent in ourselves is made by a rare inborn disease that both prevents the growth of the sex organs and abolishes the sense of smell, suggesting that the two systems share a common pathway of development in the early embryo.
Variation in the way we look, see, smell and taste is but a tiny part of the universe of difference. The genes that enable mice to recognise each other by scent are part of a larger system of identifying outsiders. The threat of infection means that every creature is always in conflict with the external world. The immune system determines what should be kept out. It differentiates ‘self’ from ‘not-self’ and makes protective antibodies that interact with antigens (chemical clues on a native or foreign molecule) to define whether any substance is acceptable. The millions of antibodies each recognises a single antigen. Cells bear antigens of their own that, with great precision, separate each individual from his fellows. Antigens are a hint of the mass of uniqueness beneath the bland surface of the human race.
When blood from two people is mixed, it may turn into a sticky mess. The process is controlled by a system of antigens called the blood groups. Only certain combinations can mix successfully. Some groups, ABO and Rhesus for example, are familiar, while others, such as Duffy and Kell, are less so. Because of their importance in transfusion, millions of people have been tested. A dozen systems are screened on a routine basis and each comes in a number of forms. This small sample of genes generates plenty of diversity. The chances of two Englishmen having the same combination of all twelve blood groups is only about one in three thousand. Of an Englishman and a Welshman it is even less and of an English person and an African less again.
Since the discovery of the blood groups and other cues on the surfaces of cells, there has been a technical revolution. Like the stone age revolution a thousand centuries ago, it depends on simple tools that can be used in many ways. The DNA of different people can now be compared letter by letter, to test how unique we are. The Human Genome Diversity Project is a spin-off from the main mapping effort which has tested thousands of people. On the average, and depending on what piece of the DNA is tested, two people differ in about one or two DNA letters per thousand; that is, in about three to six million places in the whole inherited message. Some of the differences involve changes in single bases (single nucleotide polymorphisms, or ‘snips’ as they are called), some in the number of short repeats of particular sequences (‘microsatellites’ and ‘minisatellites’) and some turn on the presence or absence of bits of mobile DNA that leapt into a particular place in the genome long