To paraphrase Mark Twain, reports of the impending death of the human Y chromosome have been greatly exaggerated.
Research published last week revealed that the chromosome of maleness -- which under the microscope looks as worn down and misshapen as a stubbed-out cheroot -- is actually healthy and holding up fine against the ravages of evolutionary time.
It turns out the human Y has barely changed in the last 6 million years. All its important parts still work. Predictions that it will cease to exist in another 10 million years -- and with it, men as we know them -- may be wrong.
This news comes from a comparison of Y chromosomes in human beings and chimpanzees. It is just one of many insights arising from the side-by-side inspection of the genes of man and his closest animal relative.
Chromosomes are long strands of DNA that contain the genes instructing cells how to make RNA and proteins, the stuff of life. Human beings have 23 pairs of chromosomes, one inherited from each parent. One of these pairs is the so-called sex chromosomes, one of whose members is designated X and the other Y. Women have two X's; men have an X and a Y.
The X-Y chromosome pair is unique in that its two halves aren't remotely similar in appearance and content, as is the case in the other 22 pairs. The X is big and contains about 1,000 genes. The Y is squat and contains only 78. Curiously, though, they are descended from the same "ancestor chromosome," which existed 300 million years ago at the dawn of this form of sexual reproduction.
Since then, the Y has thrown out most of the genes it once had -- and that the X still has -- like a shelf of unwanted cosmetics. It has concentrated on what it does best, providing the recipe of how to make sperm.
This evolution of the Y has brought with it unique risk. When chromosomes copy themselves, as they do when cells divide, errors occasionally creep in. When this occurs in the 22 matched pairs of chromosomes, or in the X-X pair that women possess, a damaged gene in one member of the pair can be cut out and replaced with a good one in the other member. But men are X-Y. Their Y chromosome never has a "brother" to recombine with, so this kind of repair can't happen.
Two years ago, research by David C. Page's laboratory revealed that the genes devoted to sperm production on the Y have a different way of preserving themselves. The sperm genes exist in duplicate form such that the chromosome can fold over on itself and swap and splice pieces from different sections in much the same way the two members of a chromosome pair do.
Despite this mechanism, some scientists believe the huge shrinkage of the Y over evolutionary time means it is inherently unstable and will eventually wither away.
Now, it appears that this isn't happening -- at least in the case of the human Y.
This evidence, too, comes from the laboratory headed by Page, a molecular geneticist at the Massachusetts Institute of Technology and the Howard Hughes Medical Institute. He, an MIT postdoctoral researcher named Jennifer F. Hughes, and collaborators at Washington University in St. Louis described their findings last week in the journal Nature.
They looked at the few genes on the Y that are not directly involved in sperm production, all of which have counterparts on the X. They reasoned that if the Y was destined to decay further, some of the non-sperm genes that humans and chimps once shared on their Y chromosomes would have disappeared in the 6 million years since the two species diverged. What they found, however, was that all 16 of the non-sperm genes on the human Y had counterparts on the chimp chromosome. There were no genes on the chimp Y that were not also represented on the human Y. The researchers concluded no genes have been lost on the path to humanness.
Page believes it is because natural selection -- the driving force of evolution -- is simply powerful enough to preserve even the Y's highly vulnerable non-sperm genes.
He theorizes that when a mutation occurs in one of those genes, it may somehow make a man slightly less fertile or "fit" even if it isn't directly involved in sperm production. If that is true, then those men will tend to have fewer offspring over time than men with intact Y genes. The mutant-Y lineages, although they might survive for a while, would be out-competed by the intact-Y lineages and die out.
However, this Y-preserving scenario is clearly not absolute, because most of the Y has in fact disappeared over the last 300 million years. And, curiously, in the chimpanzee -- but not in the human being -- it has continued to disappear in the last 6 million.
Page and his collaborators found that five of the 16 non-sperm genes in the chimp were no longer active. Mutations had killed them.
What could possibly have made that happen?
Page doesn't know, but he has a guess.
Chimpanzees are sexually promiscuous. Females mate with multiple males. Just as males compete with each other for territory on the ground, billions of their sperm compete inside the female's genital tract as they race to fertilize the egg.
If a mutation occurs in a sperm-producing gene on the Y that leads the chimp to make more or faster sperm, the mutation will tend to be preserved over evolutionary time. It will be preserved even if, by chance, it is accompanied by a damaging mutation in one of the Y's non-sperm genes. The work done by that killed gene would probably be made up by their "cousin" genes on the X.
Page speculates this may be what happened with the chimpanzee.
If he is right, it is an example of how behavior -- in this case, chimpanzee sexual promiscuity -- has shaped the species's genome. The traditional assumption has been the opposite, namely that genes drive behavior.
"I think we had a simple-minded idea that once we knew the DNA sequence of the genome, we could read out behaviors as if we were looking at a cookbook. But the connection between our genomes and our behaviors works in both directions," he said.
So is the Y out of the woods? Will it live forever despite its long history of decay?
Huntington F. Willard, director of the Institute for Genome Sciences and Policy at Duke University, said he thinks the theory of the Y's "impending demise" is still viable. It may simply be that the chimp Y is closer to its end than the human one.
Sexual reproduction is not likely to disappear, Willard believes. But the current method, which requires a Y chromosome, just might.