Dosage compensation in Drosophila in the 1960s: a personal historical perspective

Early genetic studies with Drosophila revealed similar mutant phenotypes for many X-linked genes, in males with one and in females with two copies of the mutant allele following the XY/XX mode of sex determination. These observations led to evocation of the phenomenon of dosage compensation. By the 1960s, contrasting theories were advanced by H. J. Muller and R. B. Goldschmidt to explain the equalized expression of many X-linked genes despite their dosage difference in male and female flies. Evidence from genetic studies led Muller to propose existence of many modifiers whose action on individual X-linked genes resulted, through a 'piecemeal' regulation, in equalized expression of the dosage compensated X-linked genes, while Goldschmidt believed that invocation of multiple modifiers or compensators was unnecessary since dosage compensation was a direct outcome of the sex-specific physiologies of male and female flies. Muller did not agree with some cytological studies that suggested that the single X-chromosome in male cells works twice as hard as each of the two X-chromosomes in female cells (hyperactive male X model), but preferred partial repression of each X-chromosome in female flies. This historical perspective relates these divergent theories with my own doctoral work in A. S. Mukherjee's laboratory at Calcutta University, which, while ruling out Golschmidt's sex-physiology theory, established cell-autonomous regulation of the earlier proposed hyperactivity of the single X in male Drosophila in a piecemeal manner.