Indiana, published his first scientific paper on genes in 1911, and a veritable flood of ideas and experiments followed in the succeeding decades. In 1964 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 THE ENIGMA
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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, con-versely, sex is unnecessary if you stay small. 38
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 fatal in a single cell can be easily smuggled into a bud. 39
If the ratchet is a problem only for big creatures, why do so many small ones have sex? Besides, to halt the ratchet requires only occasional episodes of sex; it does not require so many animals to abandon asexual reproduction altogether: Aware of these difficulties, in 1982 Alexey Kondrashov of the Research Computer Center in Poschino, near Moscow, came up with a theory that is a sort of reverse Muller 's ratchet. He argued that in an asexual population, every time a creature dies because of a mutation it gets rid of that mutation but no more. In a sexual population some of the creatures born have lots of mutations and some have few: If the ones with
lots of mutations die, then sex keeps throwing the ratchet into reverse, purging mutations: Since most mutations are harmful, this gives sex a great advantage.'°
But why purge mutations in this way rather than correct more of them by better proofreading? Kondrashov has an ingenious explanation of why this makes sense: The cost of making proofreading mechanisms perfect gets rapidly higher as you get nearer to perfection; in other words, it is like the law of diminishing returns: Allowing some mistakes through but having sex to purge them out may be cheaper:
Matthew Meselson, a distinguished molecular biologist, has come up with another explanation that expands on Kondrashov 's idea: Meselson suggests that 'ordinary ' mutations that change one letter for another in the genetic code are fairly innocuous because they can be repaired, but insertions—whole chunks of DNA that jump into the middle of genes—cannot be reversed so easily: These 'selfish ' insertions tend to spread like an infection, but sex defeats them, since sex segregates them into certain individuals whose deaths purge them from the population:'
Kondrashov is prepared to stand by an empirical test of his idea: He says that if the rate of deleterious mutations turns out to be more than one per individual per generation, then he is happy; if it proves to be less than one, then his idea is in trouble: The evidence so far is that the deleterious mutation rate teeters on the edge: It is about one per individual per generation in most creatures: But even supposing it is high enough, all that proves is that sex can perhaps play a role in purging mutations: It does not say that is why sex persists.' Z
Meanwhile, there are defects in the theory: It fails to explain how bacteria—of which some species rarely have sex and others not at all—nonetheless suffer from mutation at a low rate and make fewer proofreading mistakes when copying DNA: As one of Kondrashov 's critics put it, sex is 'a cumbersome strange tool to have evolved for a housekeeping role: ''
And Kondrashov 's theory suffers from the same flaw as all genetic-repair theories and the Vicar of Bray himself: It works too THE ENIGMA
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