Baker B S, Ridge K A
Genetics. 1980 Feb;94(2):383-423. doi: 10.1093/genetics/94.2.383.
Sex determination in Drosophila melanogaster is under the control of the X chromosome:autosome ratio and at least four major regulatory genes: transformer (tra), transformer-2 (tra-2), doublesex (dsx) and intersex (ix). Attention is focused here on the roles of these four loci in sex determination. By examining the sexual phenotype of clones of homozygous mutant cells produced by mitotic recombination in flies heterozygous for a given recessive sex-determination mutant, we have shown that the tra, tra-2 and dsx loci determine sex in a cell-autonomous manner. The effect of removing the wild-type allele of each locus (by mitotic recombination) at a number of times during development has been used to determine when the wild-type alleles of the tra, tra-2 and dsx loci have been transcribed sufficiently to support normal sexual development. The wild-type alleles of all three loci are needed into the early pupal period for normal sex determination in the cells that produce the sexually dimorphic (in pigmentation) cuticle of the fifth and sixth dorsal abdominal segments. tra(+) and tra-2(+) cease being needed shortly before the termination of cell division in the abdomen, whereas dsx(+) is required at least until the end of division. By contrast, in the foreleg, the wild-type alleles of tra(+) and tra-2(+) have functioned sufficiently for normal sexual differentiation to occur by about 24 to 48 hours before pupariation, but dsx(+) is required in the foreleg at least until pupariation.--A comparison of the phenotypes produced in mutant/deficiency and homozygous mutant-bearing flies shows that dsx, tra-2 and tra mutants result in a loss of wild-type function and probably represent null alleles at these genes.-All possible homozygous doublemutant combinations of ix, tra-2 and dsx have been constructed and reveal a clear pattern of epistasis: dsx > tra, tra-2 > ix. We conclude that these genes function in a single pathway that determines sex. The data suggest that these mutants are major regulatory loci that control the batteries of genes necessary for the development of many, and perhaps all, secondary sexual characteristics.-The striking similarities between the properties of these loci and those of the homeotic loci that determine segmental and subsegmental specialization during development suggest that the basic mechanisms of regulation are the same in the two situations. The phenotypes and interactions of these sex-determination mutants provide the basis for the model of how the wild-type alleles of these loci act together to effect normal sex determination. Implications of these observations for the function of other homeotic loci are discussed.
黑腹果蝇的性别决定受X染色体与常染色体的比例以及至少四个主要调控基因的控制：变异性别决定基因（transformer，tra）、变异性别决定基因-2（transformer-2，tra-2）、双性基因（doublesex，dsx）和雌雄嵌合体基因（intersex，ix）。本文重点关注这四个基因座在性别决定中的作用。通过检查在给定隐性性别决定突变体的杂合果蝇中通过有丝分裂重组产生的纯合突变细胞克隆的性表型，我们发现tra、tra-2和dsx基因座以细胞自主的方式决定性别。在发育过程中的多个时间点通过有丝分裂重组去除每个基因座的野生型等位基因，以此来确定tra、tra-2和dsx基因座的野生型等位基因何时转录足够以支持正常的性发育。在产生第五和第六腹背节具有性别二态性（色素沉着方面）表皮的细胞中，所有这三个基因座的野生型等位基因在蛹期早期都是正常性别决定所必需的。tra(+)和tra-2(+)在腹部细胞分裂终止前不久不再是必需的，而dsx(+)至少在分裂结束前都是必需的。相比之下，在前腿中，tra(+)和tra-2(+)的野生型等位基因在化蛹前约24至48小时就已充分发挥作用，以实现正常的性别分化，但前腿中dsx(+)至少在化蛹前都是必需的。——对突变体/缺失型和携带纯合突变体的果蝇所产生的表型进行比较表明，dsx、tra-2和tra突变体导致野生型功能丧失，可能代表这些基因的无效等位基因。——构建了ix、tra-2和dsx的所有可能的纯合双突变组合，揭示了一种明确的上位性模式：dsx > tra，tra-2 > ix。我们得出结论，这些基因在决定性别的单一途径中发挥作用。数据表明，这些突变体是主要的调控基因座，控制着许多甚至可能是所有第二性征发育所需的基因群。——这些基因座的特性与发育过程中决定节段和亚节段特化的同源异型基因座的特性之间惊人的相似性表明，这两种情况下的基本调控机制是相同的。这些性别决定突变体的表型和相互作用为这些基因座的野生型等位基因如何共同作用以实现正常性别决定的模型提供了基础。本文还讨论了这些观察结果对其他同源异型基因座功能的影响。
