14 August 2007

Evolution of the X and Y Chromosomes, Part 1

So far we know that dosage compensation in humans and mice involves silencing one of the two X chromosomes in XX (normally female) animals (see Part 3 of the Development Primer). But that isn't the whole story.

Dosage compensation requires either up-regulation of X expression in cells with one X chromosome, or down-regulation in cells with two X chromosomes. At first, we just compared the two Xs to each other, and saw that one was silenced while the other was expressed. But when we compare expression from the active X chromosome to a normal autosome, we see that the active X is twice as active as any autosome.

Next, consider Turner syndrome (XO women) and Klinefelter's syndrome (XXY men). These syndromes are caused by a rare event called nondisjunction. Normal human cells are diploid; that is, they have two copies of each chromosome (one from Mom, one from Dad). Gametes (sperm and egg) need to be haploid, having one copy of each chromosome. So as the cell prepares to divide during meiosis, the chromosomes are lined up in the center of the cell and are pulled in opposite directions. Normally, one chromosome of each pair goes to each side. But sometimes nondisjunction occurs; a pair of chromosomes get stuck together, so one gamete gets no copy and the other gets an extra copy (like those old Twix commercials: "Two for me, none for you!"). If those gametes then get to become part of a zygote, then the zygote will have an abnormal number of chromosomes.

If the inactive X chromosome were completely inactive, then we should expect to see no difference between XO and XX females, nor between XY and XXY males. But since Turner and Klinefelter's are syndromes, the lack of X in the former and extra X in the latter must be doing something.

As it turns out, not all the genes on the inactive X are silenced; some escape inactivation. Recall from the Development Primer that Xist-RNA forms a transcription-free zone in the nucleus, and the inactive X crawls inside. But it seems that, like a loose bundle of yarn stuck hastily in your pocket, some loops of DNA dangle out of this zone, and the genes on those loops get expressed. But which genes, and why?

At this point, we turn to research on X and Y chromosome evolution.

Stay tuned.


pauzhaan said...

As the mother of a gorgeous 18yo (atheist) daughter with Turner Syndrome (mosaic), I 'm here to tell you there most definitely is a difference between a girl with xx in every cell and a girl who is xo in half her cells and xx in the other half.

Although my child is physically outwardly beautiful, she has a major learning disability in math -- interactive mri has shown the part of her brain that "lights up" when processing math is the verbal processing part of her brain.

Her immune system tends to be low, and she's had a lot of trouble with her ears and sinus' due to congenital defects.

Nonetheless, she is an elite athlete, competing throughout the US, Europe and New Zealand in snowboarding.

I'm excited to continue reading this blog!

Aaron "Hawkeye" Golas said...

Thank you so much for sharing! I'm sorry about your daughter's troubles, but glad to hear she's excelling nonetheless. She apparently has a very supportive mother, and I know that must help. :-)