The fruit fly Drosophila melanogaster has eight chromosomes: three pairs of autosomes and one pair of sex chromosomes. Usually, females have two X chromosomes and males have an X chromosome and a Y chromosome. In the 1920s, Calvin Bridges proposed that sex in Drosophila was determined not by the number of X and Y chromosomes, but rather by the balance of female-determining genes on the X chromosome and male-determining genes on the autosomes. He suggested that a fly’s sex is determined by the so-called X : A ratio, the number of X chromosomes divided by the number of haploid sets of autosomes. Normal flies possess two haploid sets of autosomes and either two X chromosomes (females) or one X chromosome and a Y chromosome (males). Bridges proposed that an X : A ratio of 1.0 produces a female fly and an X : A ratio of 0.5 produces a male fly. He also suggested that an X : A ratio between 1.0 and 0.5 produces an intersex fly, with a mixture of male and female characteristics. An X : A ratio of less than 0.5 or greater than 1.0 produces developmentally abnormal flies called metamales and metafemales, respectively. When Bridges and others examined flies with different numbers of sex chromosomes and autosomes, the X : A ratio appeared to correctly predict the phenotypic sex of the flies (Table 4.1).
Although the X : A ratio correctly predicts the sexual phenotype, recent research suggests that the mechanism of sex determination is not a balance between X-linked genes and autosomal genes, as Bridges proposed. Researchers have located a number of genes on the X chromosome that affect sexual phenotype, but few autosomal sex-determining genes (required for the X : A ratio hypothesis) have been identified. New evidence suggests that genes on the X chromosome are the primary sex determinant. The influence of the number of autosomes on sex is indirect, affecting the timing of developmental events and therefore how long sex-determining genes on the X chromosome are active. For example, XX flies with three autosomal sets (XX, AAA) have an X : A ratio of 0.67 and develop an intersex phenotype. In these flies, the presence of three autosomal sets causes a critical developmental stage to shorten, not allowing female factors encoded on the X chromosomes enough time to accumulate, with the result that the flies end up with an intersex phenotype. The number of autosomes influences sex determination in Drosophila, but not through the action of autosomal genes, as envisioned by Bridges.