15 August 2007

Evolution of the X and Y Chromosomes, Part 3

Last time, we looked at how Lahn & Page determined the evolutionary ages of various regions of the X chromosome. Since then, more refined techniques have distinguished the following evolutionary strata in the X chromosome:



PAR stands for pseudo-autosomal region. This is a tiny region of DNA that still allows recombination between the X and Y chromosomes; that means the PAR retains high homology between the X and Y. The strata are numbered in order of evolutionary age; S1 is the oldest (in terms of divergence from Y), S5 is the youngest.

A 2005 paper by Carrel et. al. looked at a whole bunch of genes on the X chromosome, where they were, and whether they escaped X-inactivation. This resulted in the following figure, which shows the amount of escape from inactivation for each stratum:



The red end of the spectrum represents inactivated genes; the purple end represents genes that escape inactivation. Basically, the further away you get from the PAR, the fewer genes you'll find that have escaped X-inactivation.

It's important to note that the genes that escape X-inactivation don't necessarily have high Y-homology themselves; sometimes they just hang out with other genes that have high homology and ride their coattails.

So finally, what does this all tell us about how dosage compensation evolved in mammals? Recall that the active X is hyperactive compared to autosomes. When genes started decaying on the inverted pseudo-Y, the male cells started ramping up expression from their other X chromosome to compensate. But this heightened X expression carried over to females, too. That meant the female cells were getting too much X expression; to compensate, they evolved a mechanism for silencing one of their chromosomes.

Conclusion:
We noted that, though dosage compensation in mammals occurs via inactivation of one of the two X chromosomes in XX cells, some genes escape X-inactivation. Furthermore, expression from the active X is twice as great as expression from the autosomes. We wanted to know how this ties into evolution of the X and Y chromosomes.

X and Y homology experiments have demonstrated that the X chromosome can be broken into a pseudo-autosomal region plus five evolutionary strata based on time since divergence from the Y chromosome.

It turns out that genes found in regions with higher Y-homology are more likely to escape X-inactivation. This tells us that gene silencing likely evolved as a response to up-regulation of X expression, which in turn evolved in response to degradation of homologous genes on the pseudo-Y.

This is, of course, a fairly general model. There are exceptions, genes with homology that are silenced and genes without homology that escape silencing. But we still see a profound evolutionary trend. It goes to show that evolution isn't just about inventing genes for new proteins; it's also about changing regulation of the genes you already have.

1 comment:

archaeozoo said...

I am a new reader who arrived at this post via the Tangled Bank blog carnival. I would just like to applaud all three parts of this blog for their clear and concise explanation. Well done.