Following are two articles about us men and the apparent fragility of our chromosomal integrity. Apparently, we’re lucky to be alive and, more importantly, we are apparently no longer needed for procreation.
We can, thankfully, remove one threat to the future existence of the human male from our worry list: The male Y chromosome, after dwindling from its original robust size over millions of years, apparently has halted its disappearing act.
But don’t start cheering yet. Contrary to cultural assumptions that boys are stronger and sturdier, basic biological weaknesses are built into the male of our species. These frailties leave them more vulnerable than girls to life’s hazards, including environmental pollutants such as insecticides, lead and plasticizers that target their brains or hormones. Several studies suggest that boys are harmed in some ways by these chemical exposures that girls are not. It’s man’s fate, so to speak.
Boys are also more than two-thirds more likely than girls to be born prematurely – before the 37th week of pregnancy. And, despite advances in public health, boys in the 1970s faced a 30 percent higher chance of death by their first birthday than girls; in contrast, back in the 1750s, they were 10 per cent more likely than girls to die so early in their lives.
What is up here? Why do boys face such a burden of physical challenges?
The answer is that the male’s problems start in the womb: from his more complicated fetal development, to his genetic makeup, to how his hormones work.
The nine-month transformation from a few cells to an infant is a time of great vulnerability. Many chronic illnesses are seeded in the womb. In our species, the female is the default gender, the basic simpler model: Humans start out in the womb with female features (that’s why males have nipples). The complicated transformation in utero from female to male exposes the male to a journey packed with special perils. When the first blast of testosterone from the Y gene comes along at about the eighth week, the unisex brain has to morph into a male brain, killing off some cells in the communication centers and growing more cells in the sex and aggression centers. The simpler female reproductive system has to turn into the more complex male reproductive tract, developing tissues such as the testis and prostate. Further, it takes a greater number of cell divisions to make a male; with each comes the greater risk of an error as well as the greater vulnerability to a hit from pollutants.
On top of that challenge, the human male’s XY chromosome combination is simply more vulnerable. The two XXs in the female version of our species offer some protection: In disorders where one X chromosome has a genetic defect, the female’s healthy backup chromosome can take over. But with his single X chromosome, the male lacks a healthy copy of the gene to fall back on. The X chromosome, which never shrank, is also a larger chromosome “with far more genetic information than the Y chromosome,” finds Irva Hertz-Piciotto, a University of California, Davis autism researcher, “so there may be some inherent loss of key proteins for brain development or repair mechanisms in boys.” This is a clue to the higher autism rate among boys, she asserts.
Females also have a stronger immune system because they are packed with estrogen, a hormone that counteracts the antioxidant process. “Estrogen protects the brain; it’s a no-brainer, pun intended,” explains Theodore Slotkin, professor of neurobiology at Duke University’s School of Medicine. “It repairs and replaces, even after neural injury.” Low estrogen even leaves boys more sensitive to head injuries. The male brain “is simply a more fragile apparatus, more sensitive to almost all brain insults,” lead poisoning expert Herbert Needleman told writer Julia R. Barrett of Environmental Health Perspectives.
It’s the high levels of testosterone in the womb at critical times in gestation, according to British psychopathologist Simon Baron-Cohen, that are responsible for what he calls “the extreme male brain” – the kind exhibited by autistic boys – low in empathy, high in systematizing. And, in fact, recent decades of U.S. research do find unusually low estrogen and high testosterone levels among boys with autism.
If the balance of hormones is out of whack in males, what made that happen? Researchers are coming up with some clues.
Men, or at least male biologists, have long been alarmed that their tiny Y chromosome, once the same size as its buxom partner, the X, will continue to wither away until it simply vanishes. The male sex would then become extinct, they fear, leaving women to invent some virgin-birth method of reproduction and propagate a sexless species.
The fear is not without serious basis: The Y and X chromosomes once shared some 800 genes in common, but now, after shedding genes furiously, the Y carries just 19 of its ancestral genes, as well as the male-determining gene that is its raison d’être. So much DNA has been lost that the chromosome is a fraction of its original size.
But there are grounds for hope that the Y chromosome has reached a plateau of miniaturized perfection and will shrivel no more. Researchers led by Jennifer F. Hughes and David C. Page of the Whitehead Institute in Cambridge, Mass., have reconstructed the Y chromosome’s past and find that its gene-shedding days seem to be over. Men are not living on borrowed time after all, they reported on Wednesday in the journal Nature.
In people, sex is determined by a single gene that resides on the Y chromosome. Chromosomes come in pairs, with one set bequeathed by each parent, and the Y is paired with X such that men have an X-Y pair and women an X-X. When the male-determining gene first arose, some 320 million years ago, the X and Y were both full-length chromosomes, each bearing the same set of 1,000 or so genes.
The Y chromosome began its self-sacrificing downsizing in the gallant cause of protecting women. As is well known, the purpose of sex is to exchange DNA between the mother’s and father’s version of each gene, creating novel combinations that will help children adapt to a new environment better than their parents did. So before generating sperm and eggs, the two members of each pair of chromosomes line up side by side and swap large chunks of DNA.
But the male-determining gene on the Y cannot be allowed to sneak across onto the X because it would insert maleness where it should not be. So a no-swapping zone was created around the male-determining gene. That inhibitory zone was extended in five stages until it covered the whole of Y chromosome except its very tips.
Genes at the tips of the Y exchange DNA with the X in the usual way, but all those in between were condemned to a monklike existence. And being unable to innovate, most of these genes became first antiquated and then dispensable. The X chromosome now has 790 genes in its no-swap zone, according to best current estimates, but the Y retains a mere 19 of these original genes.
As the only part of the human genome that never passes through a woman’s body, the Y is the ideal refuge for male-favoring genes, especially those having to do with sperm production. Eight such genes have leapt onto the Y from other chromosomes, bringing its total score to 27. But these few additions have not allayed concern about the chromosome’s long-term viability.
The Whitehead team’s new report provides solid assurance by showing that the Y’s shedding of genes is not a continuing process. Almost all of its genetic self-sacrifice occurred in the distant past.
This insight was gained by decoding the Y chromosome of rhesus monkeys, which shared a common ancestor with humans at the time, and retain 20 ancestral genes, meaning those that have a counterpart gene on the X. Only one of these genes has been lost in humans at some time in the last 25 million years, showing that the Y chromosome became essentially stabilized long ago.
“It’s my sincere hope that this article might put the notion of the disappearing Y chromosome to rest,” Dr. Page said.
He and his colleagues have reconstructed the entire history of the Y chromosome, showing that its no-swap zone expanded in five stages, of which the first began 320 million years ago and the last ended 29 million years ago. Each stage was caused when a chunk of DNA fell out of the Y chromosome and was accidentally flipped the wrong way when it was patched back in, so it would no longer line up correctly with its counterpart region on the X. At each stage, loss of genes was precipitous at first but then leveled off.
The first stage originated to fence in the male-determining genes. The driving force for creating more no-swap zones was probably the existence of genes in nearby regions that were beneficial for males and detrimental for females, Dr. Page said. Sexually antagonistic genes probably exist throughout the genome, but only on the Y chromosome can the male-favoring ones gain protection.
Finally, sperm cells have been cloned from stem cells- the ultimate insult to the male!