FEATURE ARTICLE
Tracking Down a Cheating Gene
Some genes will play dirty to gain a selective advantage
Barry Ganetzky
Responders
Our recent results are the outcome of studies that I began more than 20 years ago, when I was a graduate student in Sandler's laboratory at the University of Washington. I set out to generate chromosomes from which either the Sd or the Rsp gene was deleted by exposing the chromosomes to x rays. The resulting small deletions would be useful in precisely pinpointing the chromosome location of these genes and in characterizing their functional properties.
I showed that when the Sd gene was deleted from an SD chromosome, the deleted chromosome was no longer able to distort a sensitive partner chromosome; both chromosomes were then transmitted to offspring in normal ratios. This result demonstrated that the Sd mutation caused some new function to be acquired. (This is in contrast with most genetic mutations, which cause some normal function to be lost.) When the gene producing this novel activity was completely eliminated by a deletion, an otherwise intact SD chromosome lost all ability to cause distortion.
Furthermore, when Rsps was deleted from the partner chromosome, it was no longer subject to distortion by SD. Instead, it was transmitted normally, as though it carried the Rspi gene. These results supported the idea that as a consequence of some action of Sd, the chromosomes in a spermatid nucleus that receive the Rsps gene fail to condense properly during sperm maturation. A chromosome that entirely lacks Rsp is immune to the effects of Sd. Interestingly, Rsp does not appear to have any essential function of its own. Even flies that are missing Rsp from both chromosomes are viable and fertile.
Additional studies allowed me to determine exactly where on the chromosome these genes lie. Rsp turns out to be very close to the center of the chromosome, near a structure called the centromere, which is important for chromosome movement during cell divisions—during, for example, meiosis. This particular chromosomal region contains mostly heterochromatin, highly repetitive, simple DNA sequences that generally do not code for protein. Nevertheless, heterochromatin constitutes about one-third of the total length of the chromosome. The precise function of heterochromatin is still unknown, although it is thought that this region has some structural role and may be involved in meiosis.
The location of Rsp in heterochromatin was consistent with its genetic behavior as some kind of target for the action of Sd, rather than as a typical gene encoding a protein product.
This result was confirmed by a molecular analysis by Chung-I Wu at the University of Rochester and Terrence W. Lyttle at the University of Hawaii. They successfully cloned and sequenced Rsp and showed that it does not code for a protein. Instead, Rsp is composed of a simple DNA sequence, containing 120 nucleotide bases, repeated over and over again for its entire length. Furthermore, they found that the sensitivity of Rsp to the action of Sd is a direct consequence of the number of times this sequence is repeated. The insensitive variant of Rsp, Rspi, contains fewer than 50 copies of this sequence. The sensitive variant, Rsps, contains several hundred copies, and the supersensitive variant, Rspss, contains about 1,000. The sensitive variants are so large that Sergio Pimpinelli and Patrizio Dimitri at the University of Rome have shown that these DNA segments can be seen under the microscope as a discrete blocks of heterochromatin.
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