For Motherly X Chromosome, Gender Is Only the Beginning

Great article:

By NATALIE ANGIER
Published: May 1, 2007

As May dawns and the mothers among us excitedly anticipate the clever e-cards that we soon will be linking to and the overpriced brunches that we will somehow end up paying for, the following job description may ring a familiar note:

Must be exceptionally stable yet ridiculously responsive to the needs of those around you; must be willing to trail after your loved ones, cleaning up their messes and compensating for their deficiencies and selfishness; must work twice as hard as everybody else; must accept blame for a long list of the world’s illnesses; must have a knack for shaping young minds while in no way neglecting the less glamorous tissues below; must have a high tolerance for babble and repetition; and must agree, when asked, to shut up, fade into the background and pretend you don’t exist.

As it happens, the above precis refers not only to the noble profession of motherhood to which we all owe our lives and guilt complexes. It is also a decent character sketch of the chromosome that allows a human or any other mammal to become a mother in the first place: the X chromosome.

The X chromosome, like its shorter, stubbier but no less conspicuous counterpart, the Y chromosome, is a so-called sex chromosome, a segment of DNA entrusted with the pivotal task of sex determination. A mammalian embryo outfitted with an X and Y chromosomal set buds into a male, while a mammal bearing a pair of X chromosomes emerges from the maternal berth with birthing options of her own.

Yet the X chromosome does much more than help specify an animal’s reproductive plumbing. As scientists who study the chromosome lately have learned, the X is a rich repository of genes vital to brain development and could hold the key to the evolution of our particularly corrugated cortex. Moreover, the X chromosome behaves unlike any of the other chromosomes of the body — unlike little big-man Y, certainly, but also unlike our 22 other pairs of chromosomes, the self-satisfied autosomes that constitute the rest of our genome, of the complete DNA kit packed into every cell that we carry. It is a supple, switchbacking, multitasking gumby doll patch of the genome; and the closer you look, the more Cirque du Soleil it appears.

Although the precise details of its chemical structure and performance are only just emerging, the X chromosome has long been renowned among geneticists, who named it X not because of its shape, as is commonly presumed — the non-sex chromosomes also vaguely resemble an “X” at times during cell division — but because they were baffled by the way it held itself apart from the other chromosomal pairs.

“They called it X for unknown,” said Mark T. Ross of the X Chromosome Group at the Wellcome Trust Sanger Institute in Cambridge. (When its much tinier male counterpart was finally detected, researchers simply continued down the alphabet for a name.) Many of the diseases first understood to be hereditary were linked to X’s span, for the paradoxical reason that such conditions showed their face most often in those with just a single X to claim: men.

Scientists eventually determined that we inherit two copies of our 23,000 or so genes, one from each parent; and that these genes, these chemical guidelines for how to build and maintain a human, are scattered among the 23 pairs of chromosomes, along with unseemly amounts of apparent chemical babble.

Having two copies of every gene proves especially handy when one of those paired genes is defective, at which point the working version of the gene can step in and specify enough of the essential bodybuilding protein that the baby blooms just fine and may never know its DNA is hemi-flawed. And here is where the Y’s petite stature looms large. Because it holds a mere 50ish different genes against its counterpart’s 1,100, the vast majority of X-based genes have no potential pinch-hitter on the Y. A boy who inherits from his mother an X chromosome that enfolds a faulty gene for a bloodclotting factor, say, or for a muscle protein or for a color receptor won’t find succor in the chromosomal analogue bestowed by Dad. He will be born with hemophilia, or muscular dystrophy, or color-blindness. But, hey, he will be a boy, for male-making is the task to which the Y chromosome is almost exclusively devoted.

In fact, it is to compensate for the monomania of the Y that the X chromosome has become such a mother of a multitasker. Over the 300 million years of evolution, as the Y chromosome has shrugged off more of its generic genetic responsibilities in pursuit of sexual specialization, the X has had to pick up the slack. It, too, has pawned off genes to other chromosomes. But for those genes still in its charge, the X must double their output, to prod each gene to spool out twice the protein of an ordinary gene and thus be the solo equivalent of any twinned genes located on other, nonsexy chromosomes.

Ah, but women, who have two X chromosomes, two copies of those 1,100 genes: What of them? With its usual Seussian sense of playfulness, evolution has opted to zeedo the hoofenanny. In a girl’s cells, you don’t see two pleasantly active X chromosomes behaving like two ordinary nonsex chromosomes. You see one hyperactive X chromosome, its genes busily pumping out twice the standard issue of protein, just as in a boy’s cells; and you see one X chromosome that has been largely though not wholly shut down, said Laura Carrel, a geneticist at Penn State College of Medicine.

Through an elaborate process called X inactivation, the chromosome is blanketed with a duct tape of nucleic acid. In some cells of a woman’s body it may be the chromosome from Dad that’s muffled, while in other cells the maternal one stays mum.

Every daughter, then, is a walking mosaic of clamorous and quiet chromosomes, of fatherly sermons and maternal advice, while every son has but his mother’s voice to guide him. Remember this, fellows: you are all mama’s boys.