Science Notes  -- Summer 1998
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Sixteen Genes on the inactivated X chromosome of a human female are known to escape inactivation. Twelve of these genes still have homologs on the Y chromosome, but only the two genes on either end of each chromosome (labeled here in green) are truly identical and still recombine with one another. The three genes labeled in gray are Pseudogenes. They are similar structurally to functional genes, but are never expressed.

GENETIC recombination happens to be a vigorous tonic for chromosomes, good for organisms, and the main point of sexual reproduction. When recombination is suppressed, genetic integrity comes tumbling down. The X chromosome can recombine along its whole length with a sister X whenever it passes through a female. The Y chromosome, however, never recombines along most of its length. Without recombination, genetic disintegration follows. Exactly why recombination is so useful remains to be plumbed. Though we may not know exactly how recombination exerts its cleansing powers, we know that without it DNA rearrangements accumulate, genes decay, and useless bits of DNA amplify.
      Mostly, cells scrupulously guard genetic integrity, but when DNA becomes useless, repetitive and devoid of genes, cells can toss it out without suffering any damage. Over time, the Y apparently lost nearly all the genes it once shared with the X. The mammalian Y is so degenerate that until recently many researchers believed that it did nothing except determine sex.
      When the Y degenerates, a male keeps only one copy of each of the thousands of genes it once shared with the X. A female still has two copies of these genes, intact on her X chromosomes. To balance dosage of gene products, it benefits the male to amplify expression of X-linked genes. Fruit flies stop at that to achieve dosage compensation. Mammals have gone one step further. Expression from the X was probably amplified in both males and females. Then it became in the females' interest to inactivate one of the Xs.
      Ultimately, these two things evolve in tandem: the Y loses its similarity with the X, and X inactivation spreads. But by what steps did (and does) this process occur during evolution? Such a question would probably be impossible to answer for mammals if the X and Y were fully differentiated as previously supposed. The genes that escape X inactivation were not considered evolutionary intermediates. They seemed to be flukes; perhaps their dosage doesn't particularly matter.
      But their dosage does matter. Why else would most of the genes that escape X inactivation in humans also have conserved Y cousins (or homologs)? The homologs on the Y--and this has been proven in the case of one gene--appear functionally interchangeable with their cousins on the X.
      Genes that escape X inactivation and have Y homologs are caught in intermediate stages of evolution. Finding trapped intermediates lets us reconstruct the pathway by which mammalian sex chromosomes have evolved, just as trapped chemical intermediates can permit the reconstruction of a biochemical pathway.
     Several Y genes that have decayed, or whose function has become limited, still have X homologs that escape X inactivation. But no cases are known in which a gene is subject to X inactivation yet has a Y homolog that remains conserved in structure and widely expressed. In other words, Y degeneration or divergence appears invariably to precede the expansion of X inactivation. Decay or divergence of genes on the Y drives the acquisition of X inactivation, not the other way around.
     Yet, the story of the Y is not solely a story of decay. Genes shared with the X have tended to be lost, but about half of the genes on the human Y arrived there relatively recently. Chromosomes are labile enough that genes can be transferred piecemeal from different places. Once something lands on the Y, genes tend to be amplified in copy number and rearranged. The new residents of the Y may be most likely to survive on the rogue chromosome if they confer male-specific advantages. Indeed, some of the newcomers to the human Y appear to help in sperm formation. This is yet another example of similar, independent evolutionary trajectories. The collection of genes on the human Y is not related to the collection on the fruitfly Y, but in each case, the Y appears to be a bastion of male-fertility factors.

CHROMOSOMES may hardly seem like a personal subject, but the X and the Y show a dramatic range of character: the two sister X chromosomes, one vivacious and airy, the other silent and bundled into itself; the deadbeat-father Y shirking its responsibilities and leaving more and more responsibility to the X; the single-mother X making do by evolving complex adaptations. Think of it as a poignant tale of fallibility--and of compensation.

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