eard the one about why it takes 100 million sperm to fertilize an egg? Because none of them will stop to ask for directions.
An alternative, and more molecularly correct, answer might be: because the egg keeps changing the lines to the yolk.
In a report that makes huevos rancheros of longstanding assumptions about the evolutionary stability, passivity and all-round dullness of the egg, as opposed to the foaming energy and vibrant mutability of the sperm, Dr. Willie J. Swanson of Cornell and his colleagues have shown that three reproductive proteins in the mammalian egg are among the most rapidly evolving molecules found anywhere in the body.
Two of these proteins, called ZP2 and ZP3, are sperm docking parts on the zona pellucida, the lustrously elaborate coat that surrounds the egg and controls passage into the egg's yolky interior, where its chromosomes reside; while the third protein, called oviductal glycoprotein, plays a still-mysterious but clearly critical role in fertilization.
All three molecules are evolving at a panting pace more typically associated with the famed changelings of the immune system than with an operation as basic and universal as the joining of gametes.
The fact that the genes encoding these female reproductive proteins are as mutable as genes designed to keep parasites at bay demonstrates that the relationship between sperm and egg, while essential to the persistence of all sexually reproducing creatures, is nevertheless a fractious one, Mars versus Venus stripped to its molecular skivvies.
"You'd think that the fusion of gametes would be so basic that it would important to conserve" over evolutionary time, said Dr. Swanson. "But it turns out that these are among the 10 percent fastest evolving genes in the genome, and they show great specificity from one species to the next."
Scientists who study the evolution of reproduction had long focused on the male half of the equation, and they had reported evidence that males were under relentless selective pressure to change and adapt, whether in the constituents of their sperm, the volume of their semen, the shapeliness and frilliness of their genitalia or any other masculine attributes, all for the sake of ensuring that their sperm is chosen.
The discovery, which appears in the current issue of The Proceedings of the National Academy of Sciences, offers the first proof that Darwinian selection drives the evolution of female reproductive proteins as well.
"For a strange set of reasons, some of them technical, some of them not, all the proteins that had been recognized as fast-changing had been male," said Dr. Mariana F. Wolfner, another author on the report. "What's neat about this paper is that it shows that the female proteins keep up with the boys."
The exact dynamic between the egg proteins and their counterparts on the sperm remain unclear.
Dr. Victor D. Vacquier of the Scripps Institution of Oceanography in San Diego, an expert in reproductive proteins, observes that scientists know a lot more about the nuances of the immune system and the workings of genes generally than they do about the details of fertilization.
Nevertheless, the basic pas de deux is thought to proceed roughly along these lines: The sperm struggles to latch onto the zona pellucida and crack the code of the egg in advance of all the other flagellating contenders; the egg doesn't like being pushed around, it wants to retain control over the terms of fusion, and so — ha ha! — it switches the code to its lock; the sperm rather testily adapts its coat to the new password; and so on, over the generations, back and forth, green eggs and spam.
"Just as there's a cat-and-mouse game between a virus and the host's immune system, so there seems to be a cat-and-mouse game between sperm proteins, and proteins in the egg," said Dr. Charles F. Aquadro of Cornell, a co-author.
But what purpose does all this cattiness and rattiness serve? The researchers said there were a couple of hypotheses to explain why the sperm and egg have so much trouble seeing eye to eye.
By one theory, the gametes may simply have different ideas about timing. The sperm wants to act fast: to fuse with a docking port on the egg and begin the so-called acrosomal reaction, the little biochemical striptease routine in which it loses its head and worms its way into the cytoplasm.
The trouble with that hasty approach, from the egg's perspective, is that every sperm in the neighborhood has the same sense of urgency, and should more than one sperm manage to get past the zona pellucida — a condition called polyspermy — the whole business is lost: no embryo can result, and the egg dies.
So the egg tries to slow things down through a deft and perpetual recasting of its armor. Granted, the overzealous sperm cells would not benefit from polyspermy either, but if each sperm is competing with all the other sperm cells to reach nuclear heaven, and if each is doomed should it fail to fertilize the egg in any case, it simply lacks the discipline, and the evolutionary incentive, to refrain from pushing.
The egg is the one that must strive for a state of monospermy, and reclaim it whenever a sperm threatens through mutational artistry to breach security. Alternatively, the egg may have more in mind than mere sperm counting; it may be judging the sperm cells as well.
The egg may be exercising a form of so-called cryptic female choice: selecting the best sperm from the batch with which to fuse. If so, then sperm cells would be under perpetual pressure either to improve themselves or to figure out a trick to subvert the capacity of the zona pellucida to reject them. And the eggs in turn would keep battling back for the right to decide their partner.
Whatever the precise spur to the conflict, the researchers have demonstrated that the genes encoding ZP2 and ZP3, as well as the oviductal glycoprotein, are under so-called adaptive selection — they're changing rapidly for a reason, rather than at random.
To prove their case, Dr. Swanson and his colleagues took advantage of the abundant amount of sequence information available in genetic databases, with sequences for the relevant egg proteins spelled out for mammals as diverse as macaques, house cats, house dogs, house mice, sewer rats, marmosets, baboons, sheep and humans.
Researchers looked at the egg genes across a variety of species, and used novel statistical tools developed by Dr. Ziheng Yang of University College in London that compared different types of sequence changes in different regions of each gene. They then were able to show that the number of changes in the coding regions of the gene — the important segments that inscribe the working parts of the protein — significantly exceeded the changes in the neutral, noncoding portions of the gene.
In other words, this wasn't a case of mere genetic drift and mutational slop at work; there was selective pressure to change in those parts of the genes that really counted — the parts responsible for the shape of the egg's gateway to tomorrow.
Yet, lest there be despair over this latest sign of the pervasiveness of the war between the sexes, the researchers suggest that the pressure and counterpressure on the gametes to change their recognition proteins could be one of the engines powering speciation.
In short, the staggering biological diversity that makes the world worth inhabiting could owe as much to conflict between sperm head and egg sheath as it does to other presumed sources of species divergence, like geological and climate change, or the race between predator and prey.
Where better to declare a new border between fissioning species than at the site where sperm and egg so warily fuse?
Over easy at last!
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