The geneticists, too, are obsessed with damaged DNA. But whereas the molecular biologists concentrate on the damage that is repaired, the geneticists talk about the damage that cannot be repaired. They call this " mutation. "
Scientists used to think of mutations as rare events. But in recent years they have gradually come to realize how many mutations happen. They are accumulated at the rate of about one hundred per genome per generation in mammals. That is, your children will have one hundred differences from you and your spouse in their genes as a result of random copying errors by your enzymes or as a result of mutations in your ovaries or testicles caused by cosmic rays. Of those one hundred, about ninety-nine will not matter: they will be so-called silent or neutral mutations that do not affect the sense of genes. That may not seem many, given that you have seventy-five thousand pairs of genes and that many of the changes will be tiny and harmless or will happen in silent DNA between genes. But it is enough to lead to a steady accumulation of defects and, of course, a steady rate of invention of new ideas."
The received wisdom on mutations is that most of them are bad news and a good proportion kill their owners or inheritors (cancer starts as one or more mutations), but that occasionally among the bad there is a good mutation, a genuine improvement. The sickle cell anemia mutation, for example, can be fatal to those who have two copies of it, but the mutation has actually increased in some parts of Africa because it gives immunity to malaria.
For many years geneticists concentrated on good mutations and viewed sex as a way of distributing them among the population, like the cross-fertilization of good ideas in universities and industries: Just as technology needs sex to bring in innovations from outside, so an animal or plant that relies on only its own inventions will be slow to innovate: The solution is to beg, borrow, or steal the inventions of other animals and plants, to get hold of their genes in the way that companies copy one another s inventions. Plant breeders who try to combine high yield, short stems, and disease resistance in rice plants are acting like manufacturers with access to many different inventors. Breeders of asexual plants must wait for the inventions to accumulate slowly within the same lineage: One of the reasons the common mushroom has changed very little over the three centuries that it has been in cultivation is that mushrooms are asexual, and so no selective breeding has been possible."
The most obvious reason to borrow genes is to benefit from the ingenuity of others as well as yourself. Sex brings together mutations, constantly rearranging genes into new combinations until fortuitous synergy results. One ancestor of a giraffe, for example, might have invented a longer neck while another invented longer legs: The two together were better than either alone:
But this argument confuses consequence with cause. Its advantages are far too remote; they will appear after a few generations, by which time any asexual competitor will long ago have out-populated its sexual rivals. Besides, if sex is good at throwing together good combinations of genes, it will be even better at breaking them up. The one thing you can be sure about sexual creatures is that their offspring will be different from them, as many a Caesar, Bourbon, and Plantagenet discovered to their disappointment: Plant breeders much prefer varieties of wheat or corn that are male-sterile and produce seeds without sex because it enables them to be sure their good varieties will breed true.
It is almost the definition of sex that it breaks up combinations of genes. The great cry of the geneticists is that sex reduces linkage disequilibria: What they mean is that if it were not for recombination, genes that are linked together—such as those for blue eyes and blond hair—would always be linked together, and nobody would ever have blue eyes and brown hair, or blond hair and brown eyes. Thanks to sex, the moment the fabled synergy is found, it is lost again: Sex disobeys that great injunction: If it ain t broke, don t fix it. Sex increases randomness."
In the late 1980s there was one last revival of interest in theories of good mutation: Mark Kirkpatrick and Cheryl Jenkins were interested not in two separate inventions but in the ability to invent the same thing twice. Suppose, for example, that blue eyes double fertility, so that people with blue eyes have twice as many children as people with brown eyes. And suppose that at first everybody has brown eyes. The first mutation in a brown-eyed person to blue eyes will have no effect because blue eyes are a recessive gene, and the dominant brown-eye gene on the person s other chromosome will mask it: Only when the blue-eye genes of two of the descendants of the original mutant person come together will the great benefit of blue eyes be seen. Only sex would allow the people to mate and the genes to meet. This so-called segregation theory of sex is logical and uncontroversial. It is indeed one of the advantageous consequences of sex. Unfortunately, it is far too weak an effect to be the main explanation for sex s prevalence. Mathematical models reveal that it would take five thousand generations to do its good work and asex would long since have won the game."
In recent years the geneticists have turned away from good mutations and begun to think about bad ones: Sex, they suggest, is a way of getting rid of bad mutations. This idea also has its origins in the 1960s, with Hermann Muller, one of the fathers of the Vicar of Bray theory Muller, who spent much of his career at the University of Indiana, published his first scientific paper on genes in 1911, and a veritable flood of ideas and experiments followed in the succeeding decades. In 19 64 he had one of his greatest insights; it has come to be known as Muller s ratchet: A simplified example of it goes like this: There are ten water fleas in a tank, only one of which is entirely free of mutations; the others all have one or several minor defects. On average only five of the water fleas in each generation manage to breed before they are eaten by a fish: The defect-free flea has a one-in-two chance of not breeding. So does the flea with the most defects, of course, but there is a difference: Once the defect-free flea is dead, the only way for it to be re-created is for another mutation to correct the mutation in a flea with a defect—a very unlikely possibility. The one with two defects can be re-created easily by a single mutation in a water flea with one defect anywhere among its genes. In other words, the random loss of certain lines of descent will mean that the average number of defects gradually increases. Just as a ratchet turns easily one way but cannot turn back, so genetic defects inevitably accumulate. The only way to prevent the ratchet from turning is for the perfect flea to have sex and pass its defect-free genes to other fleas before it dies.i6
Muller s ratchet applies if you use a photocopier to make a copy of a copy of a copy of a document. With each successive copy the quality deteriorates. Only if you guard the unblemished original can you regenerate a clean copy. But suppose the original is stored with the copies in a file and more copies are made when there is only one left in the file. You are just as likely to send out the original as to send out a copy. Once the original is lost, the best copy you can make is less good than it was before. But you can always make a worse copy just by copying the worst copy you have.
Graham Bell of McGill University has disinterred a curious debate that raged among biologists at the turn of the century about whether sex had a rejuvenating effect. What intrigued these early biologists was if and why a population of protozoa kept in a tank with sufficient food but given no chance to have sex inevitably fell into a gradual decline in vigor, size, and rate of (asexual) reproduction. Reanalyzing the experiments, Bell found some clear examples of Muller s ratchet at work. Bad mutations gradually accumulated in the protozoa deprived of sex. The process was accelerated by the habit of this one group of protozoa, the ciliates, of keeping its germ-line genes in one place and keeping copies of them elsewhere for everyday use. The method of reproducing the copies is hasty and inaccurate, so defects accumulate especially fast there. During sex, one of the things the creatures do is throw away their copies and create new ones from the germ-line originals. Bell compares it with a chair maker who copies the last chair he made, errors and all, and returns to his original design only occasionally. Sex therefore does indeed have a rejuvenating effect: It enables these little animals to drop all the accumulated errors of an especially fast asexual ratchet whenever they have sex."
Bell s conclusion was a curious one. If a population is small (less than 10 billion) or the number of genes in the creature is very large, the ratchet has a severe effect on an asexual lineage. This is because it is easier to lose the defect-free class in a smaller population. So those creatures with larger genomes and relatively smaller populations (10 billion is twice as many people as there are on Earth) will be ratcheted into trouble fairly quickly. But those with few genes and vast populations are all right. Bell reckons that being sexual was a prerequisite for being big (and therefore few), or, conversely, sex is unnecessary if you stay small.
Bell calculated the amount of sex—or, rather, of recombination—that is needed to halt the ratchet; for smaller creatures, less sex is necessary. Water fleas need to have sex only once every several generations. Human beings need to have sex in every generation: Moreover, as James Crow at the University of Wisconsin in Madison has suggested, Muller s ratchet may explain why budding is a relatively rare way of reproducing—especially among animals. Most asexual species still go to the trouble of growing their offspring from single cells (eggs). Why? Crow suggests it is because defects that would be
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