University Press (Beaumont, Tex.), Vol. 77, No. 16, Ed. 1 Wednesday, November 1, 2000 Page: 3 of 6
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University Press • Wednesday, November 1,2000 • Page 3
Scientists close to deciphering Y chromosome: Will it finally get some respect?
MALCOLM RITTER
Associated Press
Scientists are close to deci-
phering the makeup of the Y chro-
mosome, that essential core of
maleness that’s saddled with a bad
reputation, a weird past and an
uncertain future.
It’s true, guys: Millions of years
from now, your descendants might
not have a Y chromosome at all.
First things first. By this win-
ter, scientists hope to have worked
out the DNA sequence of the Y
chromosome — the identity of its
DNA building blocks. They plan
to publish their analysis of the
sequence sometime next year.
* The work should help
researchers learn about causes of
male infertility, because it’ll help
“them identify genes on the Y that
men need to make sperm.
It should also give a big push
to understanding the evolution
and functions of the chromosome,
a quest that went nowhere for
decades until just the 1980s. In fact,
one expert says earlier failures to
understand the Y have given it a
bad rap as a genetic couch potato,
and he hopes new DNA studies
will finally gain it some respect.
“There’s been almost a centu-
ry of ignorance-based misunder-
standing of the Y,” says David
Page of the Whitehead Institute in
Cambridge, Mass.
“There aren’t that many chro-
mosomes that have an intellectual
history” of thought and study by
scientists, he said. “It’s just that
most of its intellectual history
. sounds like the life story of Rod-
ney Dangerfield.”
The Y chromosome probably
didn’t get much respect from your
high school biology teacher. You
did learn that chromosomes are
the microscopic rods that hold
genes. Chromosomes generally
come in matched pairs, with one
"member of each pair from Mom
“and the other from Dad.
Men have one wildly mis-
matched pair, the X and the Y.
jThe Y chromosome makes males.
If you inherit it from your dad,
you’ll become a boy. If you get an
X chromosome from Dad instead,
you’ll be a girl.
What else is there to say about
the Y, this dinky chromosome with
a paltry number of genes? Even
now among scientists, Page con-
cedes, beyond its sex-determining
role “the general feeling is that it’s
at best a landfill.”
Having studied it for about 20
years, Page sees it as more of a
national park, full of unusual nat-
ural features.
“There’s no doubt in my
mind,” he said, “that the Y will
stand out as much as Yosemite and
Yellowstone, stand out from the
landscape.”
The sequencing of the Y is be-
ing overseen by Page and Robert
Waterston and Rick Wilson of
Washington University School of
Medicine in St. Louis. The se-
quence will cover 20 million to 30
million of its 60 million building
blocks, because the missing por-
tion resists current sequencing
technology and appears relatively
inert anyway. Under scientific stan-
dards, the sequence will still be con-
sidered complete.
The effort is part of the
Human Genome Project, which
seeks to reveal the 3 billion chemi-
cal building blocks that make up
all 24 of the human chromosomes.
Only two chromosomes have been
completely sequenced so far by the
project, which announced in June
that it had finished a rough draft of
all the human chromosomes.
Also this summer, Celera Ge-
nomics said it had sequenced all
the human chromosomes, the col-
lection called the human genome.
But Celera shares its data only
with paying clients. So for most sci-
entists, data on the Y chromosome
sequence will come from the
efforts of Page, Waterston and
Wilson.
The idea that men had their
own chromosome was recognized
in the early 1920s, and the Y was
one of the first to be identifiable
under a microscope. But while
researchers could figure out what
kinds of genes the X chromosome
carried by studying generations of
families, this approach failed spec-
tacularly when applied to the Y.
Not that researchers didn’t try.
In the first half of the 20th century,
there were lots of claims about
physical traits that seemed to pass
from father to son, and so seemed
to arise from Y chromosome
genes. Hairy earlobes and a partic-
ular kind of scaling called porcu-
pine skin were among them, Page
noted.
At a 1957 meeting of the
American Society of Human
Genetics, the group’s president
stood up and demolished all the
claims.
“That was sort of a defining
moment in the intellectual history
of the Y chromosome,” Page
said.” At the end of his talk, there
were no genes left standing.”
For decades after that, scien-
tists regarded the Y as a wasteland,
Page said. Yes, it carried some
gene that determined gender in a
fertilized egg, “but it was otherwise
perceived to be...the empty dance
partner for the X chromosome in
males.”
That view has largely held on,
even though evidence has emerged
in the past three years that the chro-
mosome carries at least two dozen
genes or gene families. That’s mea-
ger compared to maybe 2,000 or
more genes on the X, Page con-
cedes, but it shows the Y deserves
more credit than it usually gets.
He said the Y is unique for its
degree of specialization. Nearly all
its genes do one of just two things:
help make sperm, or help cells do
essential housekeeping tasks like
build proteins. In addition, of
course, there’s the gene SRY, the
master switch that turns on the
boy-making machinery.
To understand today’s Y chro-
mosome, it helps to consider its
evolution — both where it came
from and where it’s going. That
story is inextricably linked with the
X.
“The story of the evolution of
the sex chromosomes is as rich as
any novel ever written,” Page
declares.
Here’s the plot line that has
emerged in just the past few years:
The ancestors of the human X
and the Y were a pair of identical
chromosomes. They were found
some 300 million years ago in rep-
tiles, long before mammals arose.
Genes didn’t decide sex on their
own in these creatures. They re-
sponded to some environmental cue
like temperature. That still goes on
today in turtles and crocodiles.
In a single animal, an odd
thing happened. One of those sex
genes became altered. As Page
puts it, this mutated version
became “a tyrannical male-deter-
mining gene that said, ‘I will no
longer respond to these environ-
mental cues. If I am present, the
male pathway will be followed.’ ”
This rogue gene made trouble
for its chromosome because the
other DNA in its immediate vicin-
ity became altered. Later in evolu-
tion, this zone of alteration got big-
ger and bigger.
Normally, the pairs of identi-
cal chromosomes in people and
other animals trade little bits of
corresponding DNA back and
forth. This reshuffles the genetic
deck and helps species get rid of
harmful mutations.
As that zone of altered DNA
widened around the rogue gene,
the chromosome was able to do
less and less of this trading with its
unaltered partner. As a result, the
once-identical chromosomes grew
more and more unlike over time.
In fact, they eventually became the
X and Y chromosomes.
This was a better deal for the
X than the Y. Every female inher-
ited two X chromosomes, just like
today, so those two could carry out
the DNA exchange normally. That
left the X in good shape for the
long haul.
The Y chromosome never got
a chance to pair up with another Y.
Just like today, it kept being paired
up with an X instead, in males.
And as the X and Y chromosomes
grew more dissimilar over time,
that poor Y chromosome became
less and less able to trade DNA
with its partner.
The result? Genes on the Y
began to suffer minor mutations
they couldn’t get rid of, and these
nicks and scratches built up.
“It’s like the genes are being
nickeled-and-dimed to death,”
explained William R. Rice, who
studies the Y chromosome at the
University of California, Santa
Barbara.
Eventually, these genes simply
stopped working. And once genes
stop working, they tend to disap-
pear. That’s why the Y chromo-
some is only one-third the size of
theX.
For a gene, Page notes, the Y
chromosome is a very hard place
to make a living.
And that’s the threat to the Y’s
existence in the future. It’s a toxic
neighborhood. Will any genes sur-
vive? Even the master sex switch or
the genes required for making
sperm aren’t guaranteed a free
ride. If necessary, genes on other
chromosomes might take over
their jobs, leaving them free to slip
into oblivion without taking the
human race with them.
The Y chromosome has disap-
peared in hundreds of other
species, Rice said.
There is hope for this belea-
guered chromosome: immigration.
Remember that trading bet-
ween matched chromosome pairs?
That isn’t the only way DNA can
move between chromosomes.
Genes can also jump from one
chromosome to a completely differ-
ent one. And in the last few years
scientists have discovered that dur-
ing the last 30 million to 50 million
years of primate evolution, the Y
has been an alluring destination.
The immigrants are genes that
are essential for making sperm.
That makes sense, according to
theory, because they would natu-
rally accumulate on a chromo-
some that appears only in men,
where they’d avoid any potential
side effects from operating in
women.
So, over the next 100 million
years or so, the balance between
the death of Y chromosome genes
and the arrival of new ones will
decide if the Y chromosome sticks
around.
“There’s new stuff coming on
all the time,” Rice says. The Y is
“not about to blink out.”
The Y has so few genes to jus-
tify its existence, he said, that “if
we last long enough we will proba-
bly lose it.”
Page isn’t placing any bets.
“The experiment is continu-
ing,” he said, “and its outcome is
unpredictable.”
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Cobb, Joshua. University Press (Beaumont, Tex.), Vol. 77, No. 16, Ed. 1 Wednesday, November 1, 2000, newspaper, November 1, 2000; Beaumont, Texas. (https://texashistory.unt.edu/ark:/67531/metapth500912/m1/3/?q=Lamar+University: accessed June 4, 2024), University of North Texas Libraries, The Portal to Texas History, https://texashistory.unt.edu; crediting Lamar University.