Men are different. Here's Y

Natalie Anger reports on the magic of the chromosome that takes care of male arteries and brains

By Natalie Anger
  • Published 18.06.18
  • a few seconds read

Post 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 who made you feel special yesterday.

Researchers have discovered that, contrary to long-standing 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 build-up 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 decluttering appears to put 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."

David Page of the Whitehead Institute in Cambridge, Massachusetts, US, 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 foetus, 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 programmes 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," 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, UK.

Vassiliou and his colleagues reported in May on a Y-specific gene called UT-Y that protects against leukaemia in mice and likely performs a similar role in men. The chromosome more generally is committed to its bearer's health and persistence.

Forsberg of Uppsala University, Sweden, and 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 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 per cent 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 non-demented cohorts.