From DNA to form: the achaete-scute complex.

Abstract

The large bristles of flies (macrochaetes) are sense organs that form at precise locations on the thorax and the head, so much so that each has been given a name. The first scute mutant, a fly that lacked a few bristles, was discovered in 1916. As more mutations were found, it was observed that different alleles removed different subsets of bristles. A few of the new mutations affected a subset of bristles totally different from the subset elimi­ nated by the original scute mutation, sc^. Such muta­ tions fully complement sc^ and therefore were assumed to define a new gene named achaete. Early investigators were struck by the fact that each scute allele removed a specific subset of bristles, and they set out to understand whether and how the struc­ ture of the gene could explain such specificity. One theory, originating with a group of Russian genetists (who isolated many scute mutations in the late 1920s, after Miiller discovered that X-rays are mutagenic) held that scute contained distinct subgenes, each responsible for the development of one or a few bristles (Serebrowsky and Dubinin 1930; Agol 1931; Dubinin 1932, 1933). However, western geneticists asserted that the specificity was not in scute, but resulted from regional differences in the epidermis and/or involved the genetic system as a whole (Goldschmidt 1931, 1938; Sturtevant and Schultz 1931; Child 1935). At the heart of the disagreement lay the problem of the divisibility of the gene. This was understood clearly by H. Miiller, who had worked with both sides. He dem­ onstrated that the chromosome segment affected by scute mutations contains at least three adjacent genes, two of which {achaete and scute) are essential for the formation of bristles, while the third [lethal of scute) is essential for viability (Miiller and Prokofyeva 1935). Yet, in conclusion to an outstanding piece of work that in­ volved the feat of planning and bringing to fruition 29 consecutive crosses, he admitted that there is no way to decide whether this region may be further subdivided into elements that specify individual bristles, or whether the origin of the specificity must be found else­ where (Raffel and Miiller 1940). Thus, a deadlock had been reached in 1940, with no prospect of a solution. Yet, as we shall see, it now appears that both theories contain an element of truth and reflect two different aspects of a finely engineered piece of genetic ma­ chinery.