Chromosomal close-ups

Human sex chromosomes: the in many species, the sex of an individual is determined by the chromosomal constitution of the cells in that individual. For example, in humans, both males and females have 23 pairs of chromosomes; 22 of these are the same and are called autosomes. In females, the 23rd pair consists of two identical chromosomes, denoted xx , whereas in males this pair has two different chromosomes, denoted xy . In short, males have a chromosome (the y ) that females lack.

The x and the y are called sex chromosomes. Both these chromosomes are believed to have a common ancestry, with the y getting depleted of most of its genes in the course of evolution. As a result of this 'genetic pauperisation' of the y chromosome, females have double the dose of x -linked genes than males.

Normal physiology demands that the relative doses of different genes should be the same in the two sexes for the simple reason that the sexes are identical (except in respect of genes that determine maleness or femaleness). Nature solves this problem in an ingenious manner: one or the other of the two x chromosomes in each cell of the female remains inactive. As a result of x -inactivation in the female, the male is compensated for his reduced dosage of x -linked genes.

The y chromosome does carry some genes that are also present in the x chromosome. Compensation is not required as far as these common genes go: both males and females have two copies of them. Sure enough, regions of the x chromosome that carry genes also present on the y escape inactivation.

There is yet another twist in the tale. M D'Urso and colleagues at the Institute of Genetics in Naples, Italy, have recently discovered a dna sequence on the long arm of the x chromosome that appears to encode a protein, sybl 1 , similar to other proteins known to be integrated into internal membranes of the cell ( Nature Genetics , Vol 13, 1996); the sybl 1 protein's activity depends on its concentration.

The location of the dna sequence suggested that the sybl 1 gene, like its neighbours, would be active on both the x and the y . Hybrid cells were prepared which contained an active x chromosome, an inactive x chromosome and a y chromosome. sybl 1 turned out to be expressed in the active x but not in either the inactive x or the y chromosomes. This is the first instance of an x -linked gene that is present on the y but is rendered inactive.

As a result, we have before us a hitherto unknown mode of dosage compensation, because both males and females finally end up with a single functional copy even though the gene is present on the x as well as the y . What remains to be deciphered is the gene's presence on y . Alternatively, given that the gene is present on the y , we need to find out why it does not behave like other genes that are present on both x and y .