New gene may solve the Y - and X - of sex.

New gene may solve the Y (and X) of sex

Whether a person is male or female apparently depends upon a very small portion of the Y chromosome, scientists reported last week. By using abnormal human sex chromosomes and a "Noah's ark" of Y chromosomes from other species, the international research team has cloned an area containing what they say is the gene responsible for at least the first step in sex differentiation.

Although further studies are needed to confirm the gene's exact function, its discovery -- coupled with the concurrent identification of a similar segment on the X chromosome -- should answer some fundamental questions about what determines sex in humans and other species.

Scientists from the University of Helsinki in Finland, the University of British Columbia in Vancouver and the Massachusetts Institute of Technology and the Whitehead Institute for Biomedical Research in Cambridge, Mass., report in the Dec. 24 CELL that the newly cloned segment contains the testis-determining factor gene (TDF). Scientists have said for years that there must be such a factor, a "master" protein coded by the Y chromosome that can determine sex by its presence or absence. The newly identified gene, which the authors conclude "is probably TDF," apparently resides in a DNA segment only 1.3 kilobases long. In comparison, the length of the entire human Y chromosome is about 70,000 kilobases (a standard unit of measure in genetics).

With TDF's hypothesized existence as a starting point, the researchers collected data from a wide range of chromosome studies, searching for the genetic segment most likely responsible for determining sex in developing embryos. Included in the study was material from individuals with abnormal configurations of sex chromosomes.

If developed from an egg fertilized by Y-chromosome-bearing sperm, a human embryo usually becomes obviously male. In other words, the presence of both an X and a Y chromosome normally mandates male sexual development, while two X chromosomes mean an individual will be female. But in a relatively small proportion of births, the normal course of events goes awry. For example, there are XX individuals who are essentially male, as there are XY females.

Using dozens of DNA probes that attach to specific genetic sequences, the scientists compared the structures of Y chromosomes from an XX male and an XY female. They found a small portion that "is necessary and sufficient" to induce testis formation: If present, the individual is male; if absent, female. They also found what appears to be a related gene on the X chromosome. To further pinpoint the TDF gene, the researchers looked for the same DNA sequences in other mammals, and found a "striking" degree of similarity among the species, further evidence of the newly described structure's importance.