The layers correspond to increasing levels of evolutionary divorce
between the X chromosome and its
partner, the Y chromosome, which
determines whether a person will be
male.
The findings underline the importance of the Y chromosome as a
unique piece of genetic real estate
for genes that favor males but would
be detrimental to females. Despite
this privileged source of power, however, males may be at risk from the
unavoidable obsolescence of the Y
chromosome, a process that has
driven down its number of genes
from equality to one-hundredth of
those on the X chromosome.
The scientists, David C. Page of
the Whitehead Institute and his colleague Bruce T. Lahn, now of the
University of Chicago, report in Friday's issue of the journal Science
that they stumbled on the layers
while studying the differences between the 19 genes of which copies
are found on both the X and the Y
chromosome.
The two members of each pair had
diverged from each other genetically because the X and Y chromosome do
not exchange genetic material every
generation, as do the other 22 pairs of
human chromosomes, known as
autosomes.
This intergenerational exchange
of material, a grand reshuffling of
the genetic deck, gives each gene
slightly different properties and is
one reason children differ from their
parents.
Genes that cannot participate in the reshuffling eventually fail
to contribute to an individual's survival and disappear from the genome.
But human sex chromosomes
must be excluded from the reshuffling process, at least in the region of
the male-determining gene, to prevent this gene from sneaking into the
X chromosome and fomenting the
disaster of making everyone male.
In fact, reshuffling is prevented
not just at the male gene site but
along the whole length of the two sex
chromosomes. Only at their very tips
do the two chromosomes join during
the reshuffle waltz, the bare minimum of contact to keep them engaged as a pair.
Dr. Page and Dr. Lahn have discovered that the no-shuffle region did
not appear all at once but opened up
in four separate stages during evolutionary history.
The stages can be
dated by the number of genetic differences between the 19 pairs of
genes found on both the X and Y
chromosomes.
The first no-shuffle region appeared as long as 320 million years
ago, according to their calculations,
shortly after mammals evolved
from reptiles. Sex in reptiles is decided not by having different sex
chromosomes but, bizarrely enough,
by environmental cues. In turtles
and crocodiles, for example, the sex
of the embryo is determined by the
temperature at which it is incubated.
Presumably a sex-determining
gene activated by temperature or
some other external influence became genetically dominant in some
early mammalian ancestor, and at
the same time the first no-shuffle
zone arose around it. No-shuffle
zones can be created by the genetic
accident known as an inversion, in
which a stretch of DNA springs loose
from a chromosome and gets reinserted the wrong way around. The
inverted DNA no longer corresponds
to the DNA on its counterpart chromosome and cannot exchange genetic material with it.
Three more of these inversions
occurred as long as 170 million years
ago, 130 million years ago and 50
million years ago, with each event
expanding the region of the no-shuffle zone.
Dr. Huntington F. Willard, a medical geneticist at Case Western Reserve University, said it was fascinating that the traces of such distant
evolutionary events could be recovered from the human genome, especially ones that shed light on the logic
of its construction. "One of the biggest questions for understanding the
human gneome is whether it matters
how it was put together," he said.
"This is a glimpse that there is in
fact substantial method to the madness."
Though the lack of reshuffling
makes it hard for the Y chromosome
to keep its genes fit, it also creates a
haven for any genes that may evolve
to benefit males but harm females.
Male guppies, for example, are
brightly colored so as to attact females, but the colors also make the
fish dangerously visible to predators.
The color genes confer a net benefit
to the males but would harm female
fish.
Almost all these gaudy genes,
Dr. Page said, are located on the
guppy's Y chromosome, where they
cannot get into the female's genome.
The human Y chromosome, sad to
say, seems to contain no gaudy color-producing genes. And anyone expecting to find genes conferring special
prowess in war, baseball or math
will be disappointed: so far, at least,
the Y chromosome seems to contain
a very dull collection of genes. One
category, with counterparts on the X,
performs routine housekeeping tasks
in the cell; the other, the genes special to the Y, seem to be involved
mostly in sperm production and
male fertility.
"There has been speculation that
the cognitive differences between
males and females are hard-wired
into the Y chromosome, but there is
no evidence of that at present," Dr.
Page said.
But genes sometimes turn out to
have unexpected second functions,
and it could be that one of the boring
sperm-related genes on the Y chromosome can also turn on a suite of
more interesting genes located on
the other chromosomes.
"The Y can play a special role in
the battle of the sexes, " said Dr.
William R. Rice of the University of
California, Santa Barbara, a biologist who studies the evolution of X
and Y chromosomes. In fruit flies, he
noted, "the Y chromosome is a powerhouse in determining male fitness."
But the decay of the Y's original
complement of genes "created problems for males that the species has
had to come to grips with," Dr. Page
said. The problem is that a gene's
product must be delivered at just the
right levels. With loss of a Y gene, its
counterpart on the X had to work
twice as hard. And that meant that in
females, with two X chromosomes,
each gene now needed to work half
as hard as before, a problem that is
solved in humans by randomly
switching off one X chromosome in
each cell.
Although the X chromosome cannot reshuffle its genes when in
males, it escapes the Y's obsolescence because, when transmitted to
a man's daughters, it can exchange
genetic material with the other X
chromosome in a cell.
Dr. Page and Dr. Lahn calculated
the dates at which the 19 pairs of
genes started to diverge from each
other by counting the number of different DNA units between each pair.
The dated genes fell into four distinct
clusters. The genes occurred in an
apparently random order along the
Y chromosome, presumably because
of the several inversions that occurred there. But their counterpart
genes on the X chromosome turned
out to be nearly arranged in chronological order stretching from one end
of the chromosome to the other. "It
was if we were looking at geology in
an undisturbed sedimentary formation and these were the strata," Dr.
Page said.
ike archeologists exploring a succession of levels at a dig site, two
Boston scientists have discovered
four distinct layers of evolution in
the structure of the human X chromosome. From the chronology of the
layers, the scientists have inferred
some of the landmark events in the
evolution of sex chromosomes -- an
epic battle of the sexes that stretches
back to the dawn of mammalian
time.