[It’s not just what makes males into males. The sex chromosome
also influences health in hidden ways, some experts believe, and may
even explain why men have shorter life spans. ]
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SECRETS OF THE Y CHROMOSOME   [[link removed]]

 

Natalie Angier
June 11, 2020
New York Times
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_ It’s not just what makes males into males. The sex chromosome
also influences health in hidden ways, some experts believe, and may
even explain why men have shorter life spans. _

, Alex Eben Meyer

 

In advance of Father’s Day, let’s take a moment to sort out the
differences and similarities between “Dad jeans” and “Dad
genes.”

_Dad jeans_ are articles of sex-specific leisure clothing, long
mocked for being comfy, dumpy and elastic-waisted but lately
reinvented as a fashion trend, suitable for male bodies of all shapes
and ages.

_Dad genes_ are particles on the sex-specific Y chromosome, long
mocked for being a stunted clump of mostly useless nucleic waste but
lately revealed as man’s fastest friend, essential to the health of
male bodies and brains no matter the age.

Yes, dear fathers and others born with the appurtenances generally
designated male. We live in exciting times, and that includes novel
insights into the sole chromosomal distinction between you and
the women now prowling the aisles at the hardware
store. (“Didn’t he say he could use a new bow saw? Or some
halogen light bulbs?”)

Researchers have discovered that, contrary to longstanding
assumptions, the Y chromosome is not limited to a handful of masculine
tasks, like specifying male body parts in a developing embryo or
replenishing the sperm supply in an adult man.

New evidence indicates that the Y chromosome participates in an array
of essential, general-interest tasks in men, like stanching cancerous
growth, keeping arteries clear and blocking the buildup of amyloid
plaque in the brain.

As a sizable percentage of men age, their blood and other body cells
begin to spontaneously jettison copies of the Y chromosome, sometimes
quickly, sometimes slowly. That unfortunate act of chromosomal
decluttering appears to put the men at a heightened risk of
Alzheimer’s disease, leukemia and other disorders.

“I’m quite certain,” said Lars Forsberg, an associate professor
of medical genetics at Uppsala University in Sweden, “that the loss
of the Y chromosome with age explains a very large proportion of the
increased mortality in men, compared to women.”

Other researchers are tracing the evolution of the Y chromosome and
comparing the version found in modern men with those of our close
relatives, both living and extinct.

Takeaway A: We can drop the man-equals-caveman caricature. Although
human DNA has been found to contain vestiges of our dalliances with
Neanderthals from about 50,000 years ago, none of those genomic
imprints are on the human Y chromosome.

By the look of it, something specific to the Neanderthal Y chromosome
ultimately proved inimical to human health and survival, and so any
trace of the Neanderthal Y chromosome was ejected from the human gene
pool [[link removed]] like a poorly
matched kidney.

The immune system analogy may be particularly apt. Fernando Mendez, a
geneticist, and his colleague Carlos Bustamante of Stanford
University reported that one of the notable differences between the
human and Neanderthal Y chromosomes lies in a gene linked to
transplant rejection.

Whatever the reason for the purification of the human Y over time,
women’s equivalent X chromosome does not appear to have been
similarly cleansed, with the result that women on average may be
slightly more Neanderthal than men, which could explain our
comparative fondness for animal print shoes.

Yes, but apercu B: Hang on to the gorilla suit. From a global genomic
perspective, our closest living relative is the chimpanzee, followed
by the gorilla. When it comes to the Y chromosome, however, humans
look considerably more Magilla than Bonzo.

Kateryna Makova, director of the Center for Medical Genomics at Penn
State University, and her colleagues recently determined that if you
line up a man’s Y chromosome with a chimpanzee’s, only about 70
percent of the two spans will stick together. Align a human Y with a
gorilla’s, and 83 percent of the paired chromosomes will
comfortably conjoin [[link removed]].

Looking at nine distinct sets of genes that have been identified on
the human Y chromosome, Dr. Makova said, “eight of them are shared
with the gorilla, while only six gene families are shared with the
chimpanzee. It’s very surprising.”

The researchers propose that the observed patterns could be the result
of mating practices. Among gorillas, fertile females generally mate
with one male at a time — the local silverback. Women, too, are
mostly, though by no means unerringly, monogamous.

By contrast, female chimpanzees mate wildly and promiscuously during
each ovulatory cycle. As a rule, female promiscuity promotes sperm
competition among males, and because the Y chromosome oversees sperm
production, Dr. Makova said, the chimpanzee Y is likely evolving at
hyperspeed to keep up.

David Page of the Whitehead Institute in Cambridge, Mass., a world
authority on the male sex chromosome who could well be called the Y
Guy, believes the Y and the X “each deserve a full novel of their
own.”

Whether in the double-X format that specifies a female fetus, or the X
and Y pair found in males, the sex chromosomes stand apart from the
other 22 normal chromosome pairs, or autosomes, that constitute the
complete human genome and that are stuffed into nearly every cell
nucleus of the body.

That tendency toward molecular aloofness led to the initial
designation of the female chromosome as “X,” for strange or
unknown; the Y was simply named for the next letter in the alphabet.

The Y chromosome is a true chromosomal outlier, holding a fraction of
the number of genes found on all the other chromosomes, including the
X. Its genetic impoverishment is a legacy of its role in sex
determination.

Among our pre-mammalian forebears, an offspring’s sex was dictated
as it is today in crocodiles and turtles: not by genetics, but by
temperature.

Among turtles, if an egg develops in warm conditions, the embryo turns
female. If it’s cooler outside, the embryo becomes male.

But with the rise of internal gestation and its uniform weather
conditions, embryos needed another clue for sex development. That
demand led to the evolution of the male sex determination gene, called
sry, and the related need to keep the male and female genetic programs
segregated.

As a result, the Y chromosome on which sry was located could no longer
freely recombine and swap its pieces with its corresponding X
chromosome, as the other chromosomal pairs do to freshen things up
whenever a new egg or sperm cell is created.

Lacking the standard repair system of chromosomal recombination, genes
on the Y chromosome began to decay and were eventually tossed out or
reassigned to other chromosomes.

“The erection of ‘trade barriers’ allowed X and Y to follow
divergent paths,” Dr. Page said. “The X chromosome could continue
to recombine with another X chromosome in the making of eggs, but the
Y chromosome followed an isolationist strategy, which led to its rapid
decline.”

It’s not total isolationism: The tips of the X and Y chromosome can
still swap pieces, but most of Y is off limits to trans-chromosomal
barter and amendments.

“There’s a striking loneliness to the Y chromosome,” said George
Vassiliou of the Wellcome Trust Sanger Institute and Cambridge
University.

Nevertheless, the Y still has powers to divulge. After speculation in
the 1990s that the Y chromosome was still shrinking and might someday
vanish altogether — leaving who knows what sex determination
protocol in its wake — scientists are now confident the chromosomal
attrition has ended [[link removed]].

“It’s dynamic but stable,” said Melissa Wilson Sayres, who
studies sex chromosomes at Arizona State University. “It may lose a
gene or two, but it may also gain sequences. It’s not a dead end.”

Moreover, new research indicates that the Y chromosome can patch up
some internal problems without benefit of free trade and recombination
with the X — by shuffling around duplicate copies of genes on its
own lonely span.

The Y also holds a host of genes that have yet to be fully appreciated
or understood.

Dr. Vassiliou and his colleagues reported last month on a Y-specific
gene called UT-Y that protects against leukemia in mice
[[link removed]] and likely performs a
similar role in men. The chromosome more generally is committed to its
bearer’s health and persistence.

Dr. Forsberg of Uppsala University and his colleague Jan Dumanski have
published a series of papers about the phenomenon called L.O.Y., or
loss-of-Y, in which men’s blood and other cells mysteriously start
shedding their Y chromosomes with age.

Smoking hastens the depletion of the Y chromosome in men’s blood
cells, the researchers have found. Men with a high percentage of
Y-free cells — 10 percent or more — are at a heightened risk of
dying [[link removed]] in the near
future, compared with similarly aged men whose cells have hung onto
their Y’s.

And men with Alzheimer’s disease are more likely to be L.O.Y. men
than are their non-demented cohorts.

The researchers propose that a weakening of the immune system may
explain the many perils of L.O.Y. When white blood cells that serve as
immune sentries lose their Y chromosome, Dr. Dumanski said, their
surveillance skills falter.

They fail to clean up messes on arterial walls or to spot cancer cells
in need of destruction. They allow plaques and tangles to accrete in
the brain.

Dr. Dumanski admitted that the association between the loss of Y and
disease has yet to be definitively proved, and that much remains to be
understood about what’s driving the chromosomal loss in blood cells
and how it might be stopped.

“It’s still early, and there’s still a lot of skepticism,” he
said. “It will take a couple more years before the idea is widely
accepted, but we are quite convinced ourselves that we are right.”

At which he laughed — and admitted his extreme self-confidence could
well be the result of the Y chromosome that made him a man.

 

_Natalie Angier became a columnist for Science Times in January 2007.
Ms. Angier’s column focuses on the fundamentals of science, using
news events to explore the basic principles that govern the natural
world. She began writing for The Times in 1990, covering genetics,
evolutionary biology, medicine and other subjects._

_She was born in New York City on Feb. 16, 1958, and grew up in the
Bronx and New Buffalo, Mich. After attending the University of
Michigan for two years, she transferred to Barnard College in New
York, from which she graduated with high honors in 1978. While in
college, she studied English, physics and astronomy. At the age of 22,
she was hired as a founding staff member for Discover, the science
magazine that Time Inc. started in 1980._

_She has also been the senior science writer for Time magazine, an
editor at the women’s business magazine, Savvy, and a professor at
the New York University's Graduate Program in Science and
Environmental Reporting._

_Her first book, “Natural Obsessions” (Houghton Mifflin, 1988), an
inside look at the high-throttle world of cancer research, was named a
notable book of the year by The New York Times and the American
Association for the Advancement of Science._

_In 1991, she won a Pulitzer Prize in the category of beat reporting.
She has also received numerous other honors, among them the
AAAS-Westinghouse award for excellence in science journalism, the
Lewis Thomas Award for distinguished writing in the life sciences, the
Exploratorium public understanding of science award, the Barnard
College distinguished alumna award and membership in the American
Philosophical Society._

_Ms. Angier’s second book, “The Beauty of the Beastly” (Houghton
Mifflin, 1995), a hymn to the multitudinous, mostly invertebrate
creatures we would rather forget, has been translated into eight
languages. Her book “Woman: An Intimate Geography,” a celebration
of the female body and biology, which was published in 1999, was a
National Book Award finalist and has been translated into 24
languages. Her most recent book, “The Canon: A Whirligig Tour of the
Beautiful Basics of Science” (2007), won the Robert P. Balles prize
for critical thinking and has been translated into more than a dozen
languages._

_Her writing has also appeared in The Atlantic, Smithsonian, National
Geographic, The American Scholar, Parade, O magazine, Washington
Monthly, Geo, Slate and many other print and online magazines. Her
essays have been published in a number of anthologies, including
“The Bitch in the House,” “Sisterhood Is Forever,” “The New
Science Journalists” and “The St. Martin’s Guide to Writing.”
She was the editor of the 2002 edition of “The Best American Science
and Nature Writing” and the 2009 edition of “The Best American
Science Writing.”_

_Ms. Angier is a voting member of the usage panel of The American
Heritage Dictionary, and though she wholeheartedly believes that
languages must evolve or die, she will never vote in favor of using
“impact” as a verb._

_A version of this article appears in print on June 12, 2018,
Section D, Page 1 of the New York edition with the headline: Men
Are Different: Here’s Y._

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