Reduntant man

Submitted by Editor on Thu, 09/09/2004 - 23:35

As the puny Y chromosome continues to shrink, the male of the species is doomed to extinction. Or is he? By science reporter Stephen Cauchi.

http://www.theage.com.au/articles/2004/09/05/1094322639127.html

The Age (Melbourne)

6 September 2004

By Stephen Cauchi

It is not clothes that maketh the man, but the Y chromosome. Inside the trillions of cells that make up the human male is a strand of DNA, each one divided up into 46 packets, or chromosomes. The smallest and the most withered is a little packet called the Y chromosome. It's in bad shape.

Since our distant mammalian ancestors scurried through the undergrowth in the age of the dinosaurs, the Y chromosome has shrunk. Of the 1450 or so genes it boasted 300 million years ago, it has lost about 1400. In other words, the Y chromosome, and therefore all men, are inevitably doomed. Or are they?

In the past year, a spate of media stories has centred on the fate of the Y chromosome and men - many of them contradictory. Australian National University geneticist Professor Jenny Graves, one of the world's leading researchers of the Y chromosome, told a Jubilee Lecture at the ANU in May that the "human Y chromosome is running out of time". All Y chromosomes - including those in mammals - have a tendency to shrink over time, she said, and the human Y is no different.

"Most of the original human Y has been lost," she told those assembled. "It has lost 1393 of 1438 genes it began with 300 million years ago. At this rate it would lose the last 45 in just 10 million years."

Among those 45 genes is the crucial SRY gene, which induces the development of testes in the embryo, and therefore, the release of male hormones. No SRY gene, no man.

In her most recent paper, published in last month's Reproduction, Fertility and Development, Graves mulled over the options for men. Parthenogenesis, in which female eggs develop without being fertilised by sperm, "simply cannot happen in mammals," she wrote. Barring genetic techniques such as cloning - which, admittedly, is a possibility even today thanks to stem cell technology - "males are therefore absolutely required for human reproduction."

However, wrote Graves, "a male-less world is not a necessary consequence of losing the Y chromosome." In other words, men might survive loss of the chromosome and its essential SRY gene. But, then, they might not.

Take rats and mice. These creatures, like humans, are placental mammals. Certain rodent species, says Graves - the mole voles of eastern Europe and the country rats of Japan - have no Y chromosome and no SRY gene. Yet there are still plenty of healthy male mole voles and country rats running around. "Some other gene must have taken over the job," she told The Age. "We'd love to know what that gene is."

A group of scientists in Germany is working on the mystery. As the Y chromosome on these rats has vanished, one of its 42 surviving chromosomes has taken on the role of harbouring sex-determining genes.

Graves calls it a "proto- Y chromosome". "At the moment, it would be a new Y chromosome that you can't really pick out by looking down the microscope. But if you came back in another hundred million years or so, it would look very small and pathetic, just like our Y chromosome does today."

That's the good news - a species can withstand loss of the Y chromosome and the male sex-trigger gene. But it is also equally true, says Graves, that less lucky species have become extinct as a result, and humanity may join that list (barring some sort of cloning program or a massive frozen depository of sperm).

"The possibility of us finding a new sex-determining gene may be impossible to estimate," says Graves. "We just couldn't even guess at the number of species that have become extinct because they've run into trouble with their sex chromosomes."

However, assuming men do survive by going the way of the mole vole rat, the consequences will be interesting. "We already know that there are several candidate genes out there that could take over from SRY and there are probably lots more that we don't about that could take over from SRY," says Graves. Which one takes over is sheer chance. What's more, in a population as large as humanity, two or more different sex-determination systems based on different genes could arise.

If two groups of humans arise - each with different sex-determining genes - that would lead to two different species of humans. This has probably happened among other mammals, says Graves, including the mole vole rat.

But couldn't interbreeding keep the species as one?

"They (two groups with different sex-determing genes) could mate and they could produce viable offspring but the (offspring's) sex would be a mess. They'd be all kinds of intersexes and sterility in the offspring."

All of this assumes, of course, that the Y chromosome will die. Graves admits her 10-million-year figure has been "vigorously opposed" although she also says it may be a "conservative estimate".

Bryan Sykes, head of Human Genetics at Oxford University, argued last year that "human fertility will decay to 1 per cent of its present level in 125,000 years", a figure that makes Graves' estimate look optimistic.

And there are those who say the Y chromosome may not be doomed at all. A 40- strong team of researchers led by David Page of the Massachusetts Institute of Technology reported in the journal Nature last year that the Y chromosome had a previously unknown and elaborate back-up system for self-repair.

Most chromosomes, but not the Y, are arranged in pairs; when a gene in one goes bad, it can be replaced with a copy of the other partner's good gene. The Y chromosome appeared to have no way of preventing mutations from destroying its genes. But Page showed that there were duplicate genes on the Y arranged in eight socalled "palindromes within loops". Genes on one end of a palindrome could replace mutated twins on the other end, they claimed. The journal Science, in fact, listed this discovery as the ninth-most important find of 2003. "It seems that gene swapping between palindrome arms keeps the Y chromosome's genetic make-up stable," said a journal editorial.

However, Graves argues that the data has been misinterpreted. "They're saying, oh, the Y really undergoes sex after all. I would say well no it's not really genetic sex, it's genetic masturbation that the Y chromosome is undergoing. I think the work is marvellous but I think the interpretation is wrong. I don't believe that that (process) can work to refresh the Y and remove mutations because it's just as likely that the good copy would be replaced by a mutant than the other way around. In fact, there are arrays of dead genes on the Y that I think resulted from this process."

Indeed, in a recent paper published in the journal Reproduction, Fertility and Development, Graves said "perhaps it (gene-swapping) will even speed up the decline of the Y chromosome and the onset of a new round of sex chromosome differentiation."

Assuming humanity survives the loss of the Y chromosome, her prediction for its future remained unchanged."The hybrid intersexes or infertility in different human populations could conceivably provide the preconditions for the creation of new species of hominids (humans)."

So there you have it. The Y chromosome will die, and - notwithstanding cloning and other measures - it may take men with it. But, equally, men may survive the fall of the Y and split into several species. Either way

- it's a problem for the far future. Don't lose sleep over it.