'Dad Genes': A new discovery that explains 'Y' and how men are biologically
different from women
The Y chromosome is a true chromosomal outlier. Its genetic impoverishment is a
legacy of its role in sex determination
Father at home holding sleeping newborn baby daughter. “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.
June 12, 2018
12:24 PM EDT
The New York Times
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 men at a
heightened risk of Alzheimer’s disease, leukemia and other disorders.
The erection of 'trade barriers' allowed X and Y to follow divergent paths. 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
“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
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
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 like a poorly
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.
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.
Looking at nine distinct sets of genes that have been identified on the human Y
chromosome, 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
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, Makova said, the
chimpanzee Y is likely evolving at hyperspeed to keep up.
David Page of the Whitehead Institute in Cambridge, Massachusetts, 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.
I'm quite certain that the loss of the Y chromosome with age explains a very
large proportion of the increased mortality in men, compared to women
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
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
“The erection of ‘trade barriers’ allowed X and Y to follow divergent paths,”
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 still early, and there's still a lot of skepticism.It will take a couple
more years before the idea is widely accepted, but we are quite convinced
ourselves that we are right
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.
“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
Vassiliou and his colleagues reported in May on a Y-specific gene called UT-Y
that protects against leukemia in mice and likely performs a similar role in
men. The chromosome more generally is committed to its bearer’s health and
Forsberg of Uppsala University and his colleague Jan Dumanski have published a
series of papers about the phenomenon called LOY, or loss-of-Y, in which men’s
blood and other cells mysteriously start shedding their Y chromosomes with age.
A man smoking a cigar poses prior to the 150th running of the Belmont Stakes at
Belmont Park on June 9, 2018 in Elmont, New York
Mike Stobe / Getty
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 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 LOY men than are their
The researchers propose that a weakening of the immune system may explain the
many perils of LOY. When white blood cells that serve as immune sentries lose
their Y chromosome, 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.
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.
Source Originally New York Times - National Post