Common ground for X, Y chromosomes.

Common ground for X, Y chromosomes

The major difference between a female and a male mammal's cell is the chromosome composition. The female cell has a pair of X chromosomes, one of which is usually curled up in an inactive form, while the male cell has only one X chromosome and one, much smaller, Y chromosome. Scientists have hypothesized that these dissimilar chromosomes must share some of their genetic information-- the X and Y are though to have evolved from a common ancestral sex chromosome, and they still pair at every cell division, lining up the ends of their shorter arms. Now researchers are identifying genes that are carried on both of the sex chromosomes, Larry J. Shapiro of the Harbor-UCLA Medical Center in Torrance, Calif., reported in Los Angeles at the meeting of the American Association for the Advancement of Science.

At least two genes now appear to reside on both X and Y chromosomes of at least some mammalian species. Previously more than 100 genes had been assigned to the X chromosome, often on the basis of there being no matching gene in male cells. Only a few genes had been assigned to the Y chromosome--most of which relate to sex determination and thus have no counterpart on the normal X.

A gene located on both the X and Y mouse chromosomes was reported in the May 16 NATURE by scientists at the University of Washington in Seattle. This gene, called STS, affects the activity of an enzyme, steroid sulphatase. There had previously been confusion over whether the gene is on the X or one of the non-sex chromosomes. Elisabeth Keitges, Stanley M. Gartler and their colleagues also report that during meiosis, the cell division that produces sperm and eggs, the X and Y chromosomes can break and recombine so that they exchange the STS genes. In humans there appears to be no functional STS gene on the Y chromosome.

Another gene was reported to be shared by the human X and Y chromosomes. It encodes a cell surface molecule, called 12E7, found on most human tissues. Peter Goodfellow and his colleagues at the Imperial Cancer Research Fund in London, England, reported in 1983 that the gene is on the tip of the short arm of the human X chromosome and also on the short arm of the Y chromosome.

The genes of the tip of the X chromosome escape X-chromosome inactivation, Shapiro says. Three human genes have been mapped to this region: STS, 12E7 and the gene encoding a surface molecule, called Xg, found on red blood cells. In female cells, when the other known genes are inactivated on one of the two X chromosomes, these genes remain active. Shapiro speculates that the reason for their activity has an evolutionary origin.

The X and Y chromosomes must pair at meiosis so that they are properly distributed to the eggs and sperm. Therefore, some region of the chromosomes must be similar enough for the two chromosomes to line up properly. It now appears that the genes in this region act like genes on the non-sex chromosomes. They are not inactivated and they are able to recombine during meiosis.

Together, the recent findings offer a new view of the evolution of sex chromosomes. "Most people feel that the X and Y chromosomes were once homologous,' Shapiro says. The only difference was that the Y chromosome carried a block of genes that determined male characteristics. Because it was necessary that the entire set of "maleness' genes be inherited intact, recombination between these genes and genes of the X chromosome came to be suppressed, Shapiro suggests. He proposes that the same process that suppressed this recombination also produced the inactivation of the X chromosome in female cells. Often, scientists explain the basis for X-inactivation to be the need of male and female cells to produce the same levels of proteins whose genes are on the X chromosome, although the male cells have only one copy and the female cells have two copies. But according to Shapiro's theory, this dosagecompensation effect would be just a byproduct of a more basic phenomenon.

Shapiro also sees recombination suppression as a possible source of the size discrepancy between the X and Y chromosomes. Recombination is the process thought to continually monitor the similarity between paired chromosomes, so that they do not become too dissimilar. Shapiro says that once recombination between the X and Y was suppressed, they were free to drift apart evolutionarily. "Whenever a cell [except a sperm] has a Y chromosome, it always also has an X, so the Y is free to mutate and delete sequences, because the loss of information is always covered by the genes on the X.'