September 4, 2003
Goodbye boys: why men could soon be extinct
Leading scientist Brian Sykes believes that long-term deterioration of the Y chromosome, which contains the gene that confers maleness, means that the male species is doomed. So is the future female?
IN THE genetic aristocracy, the Y chromosome languishes pretty near the bottom. Over the past million or so years it has been shedding genes like a snake sheds its skin. Now comprising fewer than a hundred genes, compared to the bountiful 1,000-odd boasted by each of the 45 other chromosomes, it spends its life slaving away in the sweltering, destructive confines of the testes, where millions of sperm are generated every day in a frenzy of cell division.
Over each replication hangs the threat of a random genetic mutation, which can be handed down to the next generation. Unlike other chromosomes, which are paired and can exchange genetic material with each other, the lowly Y has no duplicate from which to seek repair. Slowly but surely, Y chromosomes throughout the world are being pounded into submission.
There will come a day, according to Bryan Sykes, professor of human genetics at Oxford University, when Y chromosomes will cease to exist. And since the Y chromosome contains the gene that confers maleness, that pivotal moment in human history will mark the extinction of men. “The time in which it will happen is debatable, but the process of extinction is inevitable,” insists Sykes, who puts forward the highly contentious idea of a man-free future in his book, Adam’s Curse.
Not that he is particularly bothered, since he thinks that the way humans breed — sexual selection — is steering us towards disaster anyway. Just as peacocks grow huge, exquisitely coloured tails to attract peahens, men fight for power and wealth to signal their sexual prowess, sometimes to ruinous effect. “There’s a limit on how large a peacock’s tail can be, because if it’s too big the peacock won’t fly,” Sykes says. “We have changed the world and made so many advances that there’s no limit on men’s behaviour except the destruction of the planet.”
According to Sykes, the gradual disappearance of the human male is the endgame of a process that started hundreds of millions of years ago in mammalian ancestry. While mammals have their gender fixed by a permutation of X and Y chromosomes — this is true for humans, chimpanzees, mice, marsupials — some other animals do not. Alligators, for example, are born either male or female according to the temperature at which they are incubated.
Scientists think that the X and Y chromosomes were originally a pair of Xs. The crucial split in the chromosomal family tree happened around 300 million years ago, when one of the Xs somehow acquired a gene for maleness. This acquisition appeared to herald a downward slide — the altered chromosome started slaking off its genes and gradually stopped swapping chunks of genetic material with its partner. The reclusiveness inevitably put the diminishing chromosome at risk; this swapping, called recombination, is the way that damaged chromosomes heal themselves. Over millions of years, the shrinking, lonely X became the Y chromosome that men carry around today.
And the main threat to the Y chromosome — its inability to use its neighbouring X chromosome to fix damage — lingers. “Once you isolate a chromosome from sexual recombination, it can’t repair mutations,” Sykes says. “So the genes on the Y chromosome are being battered continually. Then there’s the fact that the Y is confined to the germline cells of men, the sperm cells in the testes. These are very mutagenic places — the cells divide very fast to produce sperm, and when DNA is copied, you get mutations. It’s a double whammy.
“It’s strange. The X and Y arrangement isn’t bad, because it gives us roughly equal numbers of males and females. But it isn’t the best, because it means the Y will become extinct.”
And since the single gene that acts as the master switch for maleness, called SRY (Sex-determining Region of the Y chromosome) resides in this chromosomal cul-de-sac, that’s curtains for men.
Blessed with two X chromosomes that can recombine in harmony and so resist mutational onslaught, women do not face the same fate as their XY brothers. And why should evolution have dealt men such a dud hand? “Evolution has no eye to the future,” Sykes sums up.
Sykes, who rose to prominence two years ago by tracing the seven maternal ancestors of women, doesn’t mind a bit of controversy. Which is why he goes on to predict a timescale for his gender’s demise. He takes as his starting point the “staggeringly high number of infertile men who are infertile because of mutations in the Y chromosome”. He calculates that these alone can lead to a drop of 0.1 per cent in the fertility of the whole population every generation.
Within 125,000 years, or 5,000 generations, he reasons that fertility will be just 1 per cent of what it is today. With each successive generation, fewer Y chromosomes will emerge, and the downward spiral beckons. That is a much gloomier prospect than a previous estimate by an Australian team which calculated that the Y chromosome had lost an average of five genes every million years, and therefore could disappear completely over the next ten million years.
Saying goodbye to the Y, Sykes says, doesn’t necessarily spell the end of the human race; cloning requires no sperm, and certain assisted reproduction techniques allow even very damaged sperm to be injected directly into eggs, bypassing nature’s weeding-out process. However, boys born using sperm injection will carry the genetic faults of their father, and the attendant infertility, simply delaying a foregone conclusion.
Much better, Sykes suggests with breathtaking audacity, that the male gene should be snipped out of the ailing Y and reattached to another chromosome. He writes: “The prospects for the Adonis chromosome are excellent. It will reprieve men from the brink of extinction and guarantee them a future for several million years . . . it looks a good bet to me. I almost wish I had one myself.”
Sykes admits that his ideas are likely to provoke, but says that they are not jokes. “This is serious stuff. I think the Adonis chromosome would work,” he says. Still, they are likely to prove too much for the measured world of genetics, well-used to dismissing fantastical ideas and nightmarish visions of the future. Dr Robin Lovell-Badge, a leading developmental geneticist at the National Institute for Medical Research in London and one of the scientists who identified the SRY gene, calls it a “storm in a teacup”, and says that Sykes’s calculations are founded on untestable assumptions. “I find his reasoning slightly odd,” Lovell-Badge says. “If 1 per cent of men are infertile because of problems in the Y chromosome, you still have 99 per cent of normal fertile men. Nature tends to eliminate the Y chromosomes that reduce fertility. Except for certain assisted reproduction techniques, we tend to lose mutant Y chromosomes.” What’s left behind, he says, is perfectly capable of propagating both sexes.
He points out that the Y chromosomes in many mammalian species are very different, but, crucially, all those different versions, bar one or two, have retained the ability to set gender. “The fact that the Y chromosome can evolve and change tends to suggest that it can tolerate a lot of change without being lost,” he says. “Just because you have a high rate of mutation doesn’t mean a change in function, which seems to be sex determination.” Lovell-Badge also says that, technology aside, losing the male means losing the species. So a planet of Amazons seems most unlikely.
Another researcher, Dr David Page, from the Whitehead Institute of Massachusetts, has also thrown a lifeline to men. This summer, his team published a paper in Nature showing that the Y chromosome did have a capacity for self-repair. Huge stretches of its 51 million DNA letters are arranged in palindromes, long genetic sequences that read the same from both ends. If the two ends are brought together, the identical stretches can swap material. So, in biological terms, the Y chromosome can recombine — or have sex — with itself. Page also points out, however, that the swapping can lead to stretches of DNA being deleted.
Sykes describes this capacity for self-repair as “a pale reflection of the full-blown sexual liaisons that normal chromosomes experience. Sadly, the Y chromosome is just as lonely as ever, though we now know that it talks to itself as it spirals towards oblivion.”
And if men were erased from the landscape, what would we women do? Does a Sapphic future beckon? “I don’t know,” Sykes says. “There’s always the possibility of retaining men for entertainment. We know that sterility and entertainment between the sheets are not related.” The Adonis chromosome could come in handy for this purpose, he suggests helpfully.
“It sounds treacherous, but speaking on behalf of my genes, we’re better off on a planet without men,” Sykes concludes. “The fact that there’s sexual selection is responsible for the less pleasant aspects of this world, such as violence, wars and infanticide. It’s a fact that men commit most violent crime. Women don’t have the same genetic incentive to reproduce, so you don’t get the same problems. You just get different ones. One newspaper said that losing men meant that women’s living rooms would be piled to the ceiling with Ikea flatpacks. I suppose there would be less open-air flatulence. You’d probably have a ministry of shopping. Life wouldn’t be too bad, would it?”
Adam’s Curse: A Future Without Men, by Bryan Sykes, is published by Bantam Press, £18.99
The hunt for the sex gene
WOMEN have two X chromosomes; men have one X and one Y. The “default” gender is female, meaning that those without the SRY gene (the male gene) develop into women.
It is not until the seventh week of life in the womb that the genetic switch for maleness is thrown. It produces SRY protein, which then activates other genes. The unisex gonads are transformed into testes; one of the hormones destroys the Mullerian ducts, which would have become the Fallopian tubes, womb and vagina; a flow of testosterone protects the male reproductive organs as they form.
The rivalry between scientists to uncover the gene controlling sex differences was intense. Dr David Page studied a woman with an XY package who should have been male but was not. She was missing a large segment of DNA in her Y chromosome. Strikingly, Page found the same segment in the XX package of a male patient. It apparently suggested that, whatever the chromosomal make-up, this DNA segment, called ZFY, was instrumental in setting gender. Page published in 1987, seemingly wrapping up the hunt.
But the race was not over. Marsupials were found to have ZFY, but not on their sex chromosomes. Either they used a different method to determine sex, which was unlikely, or ZFY was not the crucial gene. In addition, other XX men were coming forward who didn’t have the ZFY gene. The breakthrough was finally made by Dr Robin Lovell-Badge and Dr Peter Goodfellow, who hit on a stretch of DNA later named SRY (Sex-determining Region on the Y chromosome). In 1991, they injected the SRY gene into mouse embryos. One was born with an XX package, which should have been female, but was not; but it did have the SRY gene. SRY had reversed the mouse’s sex, delivering ultimate proof of its function and a major coup for British science.
By Anjana Ahuja
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