Some very powerful force is at work ensuring that most versions of each gene survive and that no version changes very much. 3B
That force is almost certainly disease: As soon as a lock gene becomes rare, the parasite key gene that fits it becomes rare, so that lock gains an advantage: In a case where rarity is at a premium, the advantage is always swinging from one gene to another, and no gene is ever allowed to become extinct. To be sure, there are other mechanisms that can favor polymorphism: anything that gives rare genes a selective advantage over common genes: Predators often give rare genes a selective advantage by overlooking rare forms and picking out common forms. Give a bird in a cage some concealed pieces of food, most of which are painted red but a few painted green; it will quickly get the idea that red things are edible and will initially overlook green things: J: B. S Haldane was the first to realize that parasitism, even more than predation, could help to maintain polymorphism, especially if the parasite 's increased success in attacking a new variety of host goes with reduced success against an old variety—which would be the case with keys and locks:'°
The key and lock metaphor deserves closer scrutiny: In flax, for example, there are twenty-seven versions of five different genes that confer resistance to a rust fungus: twenty-seven versions of
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five locks. Each lock is fitted by several versions of one key gene in the rust. The virulence of the rust fungus attack is determined by how well its five keys fit the flax 's five locks. It is not quite like real keys and locks because there are partial fits: The rust does not have to open every lock before it can infect the flax. But the more locks it opens, the more virulent its effects.°
THE SIMILARITY BETWEEN SEX AND VACCINATION
At this point the alert know-it-alls among you will be seething with impatience at my neglect of the immune system. The normal way to fight a disease, you may point out, is not to have sex but to produce antibodies, by vaccination or whatever. The immune system is a fairly recent invention in geological terms. It started in the reptiles perhaps 300 million years ago. Frogs, fish, insects, lobsters, snails, and water fleas do not have immune systems. Even so, there is now an ingenious theory that marries the immune system with sex in an overarching Red Queen hypothesis. Hans Bremermann of the University of California at Berkeley is its author, and he makes a fascinating case for the interdependence of the two: The immune system, he points out, would not work without sex."
The immune system consists of white blood cells that come in about 10 million different types. Each type has a protein lock on it called an "antibody," which corresponds to a key carried by a bacterium called an "antigen: " If a key enters that lock, the white cell starts multiplying ferociously in order to produce an army of white cells to gobble up the key-carrying invader, be it a flu virus, a tuberculosis bacterium, or even the cells of a transplanted heart.
But the body has a problem. It cannot keep armies of each antibody-lock ready to immobilize all types of keys because there is simply no room for millions of different types, each represented by millions of individual cells. So it keeps only a few copies of each white cell. As soon as one type of white cell meets the antigen that fits its locks, it begins multiplying. Hence the delay between the onset of flu and the immune response that cures it.
THE POWER OF PARASITES
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Each lock is generated by a sort of random assembly device that tries to maintain as broad a library of kinds of lock as it can, even if some of the keys that fit them have not yet been found in parasites: This is because the parasites are continually changing their keys to try to find ones that fit the host 's changing locks: The immune system is therefore prepared. But this randomness means that the host is bound to produce white cells that are designed to attack its own cells among the many types it invents.
To get around this, the host 's own cells are equipped with a password, which is known as a major histocompatibility antigen. This stops the attack. (Please excuse the mixed metaphor—keys and locks and passwords; it does not get any more mixed.) To win, then, the parasite must do one of the following: infect somebody else by the time the immune response hits (as flu does), conceal itself inside host cells (as the AIDS virus does), change its own keys frequently (as malaria does), or try to imitate whatever password the host 's own cells carry that enable them to escape attention. Bilharzia parasites, for example, grab password molecules from host cells and stick them all over their bodies to camouflage themselves from passing white cells. Trypanosomes, which cause sleeping sickness, keep changing their keys by switching on one gene after another. The AIDS virus is craftiest of all.
According to one theory, it seems to keep mutating so that each generation has different keys. Time after time the host has locks that fit the keys and the virus gets suppressed. But eventually, after perhaps ten years, the virus 's random mutation hits upon a key that the host does not have a lock for. At that point the virus has won.
It has found the gap in the repertoire of the immune system ' s locks and runs riot. In essence, according to this theory, the AIDS virus evolves until it finds a chink in the body 's immune armor.42
Other parasites try to mimic the passwords carried by the host: The selective pressure is on all pathogens to mimic the passwords of their hosts. The selective pressure is on all hosts to keep changing the password. This, according to Bremermann, is where sex comes in:
The histocompatibility genes, which determine more than
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the passwords but are themselves responsible for susceptibility to disease, are richly polymorphic. There are over one hundred versions of each histocompatibility gene in the average population of mice, and even more in human beings. Every person carries a unique combination, which is why transplants between people other than identical twins are rejected unless special drugs are taken. And without sexual outbreeding, it is impossible to maintain that polymorphism.
Is this conjecture or is there proof? In 1991, Adrian Hill and his colleagues at Oxford University produced the first good evidence that the variability of histocompatibility genes is driven by disease: They found that one kind of histocompatibility gene, HLA-Bw53, is frequent where malaria is common and very rare elsewhere. Moreover, children ill with malaria generally do not have HLA-Bw53. That may be why they are
And in an extraordinary
discovery made by Wayne Potts of the University of Florida at Gainesville, house mice appear to choose as mates only those house mice that have different histocompatibility genes from their own.
They do this by smell. This preference maximizes the variety of genes in mice and makes the young mice more disease-resistant."
WILLIAM HAMILTON AND PARASITE POWER
That sex, polymorphism, and parasites have something to do with one another is an idea with many fathers. With characteristic pre-science, J: B. S: Haldane got most of the way there: "I wish to suggest that [heterozygosity] may play a part in disease resistance, a particular race of bacteria or virus being adapted to individuals of a certain range of biochemical constitutions, while the other constitutions are relatively resistant. " Haldane wrote that in 1949, four years before the structure of DNA was elucidated." An Indian colleague of Haldane's, Suresh Jayakar, got even closer a few years later.46 Then the idea lay dormant for many years, until the late 1970s when five people came up with the same notion independently of one another within the space of a few years: John Jaenike of THE POWER OF PARASITES