"New York Times" 27 Feb. 2001
New Rules in Sperm and Egg's Cat-and-Mouse Game

By Natalie Angier

Heard 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 andall-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!

POWRÓT