Distorted Sex Ratios: A Window into RNAi-Mediated Silencing

I n 1925, Gershenson started laboratory cultures from 19 female Drosophila obscura that were collected from a forest near Moscow. After recounting his difficulties raising the flies (partial success achieved with a diet of potatoes and fermented raisins), he noted that progeny from most cultures contained an approximately equal sex ratio [1]. Several cultures, however, yielded progeny with highly skewed ratios, such as one group with 87 females and only 7 males. These " deviations from the normal sex-ratio were so considerable that it seemed impossible to explain them by accidental causes, " he wrote. Similar observations had been made by others, but Gershenson went on to perform a number of experiments and reached three important conclusions. First, sex-ratio distortion (referred to hereafter as sex-ratio) was associated with the X chromosome. Second, the expression of the phenotype was sex-limited, because it only occurred in the progeny of males carrying the causal X chromosome. And third, the low numbers of males did not appear to be caused by preferential death of male zygotes or their transformation into females. Rather, he concluded that " the greater part of the spermatozoa determining the development of males do not participate in fertilization ". Because females have two X chromosomes and males are XY, he further suggested that either Y-bearing sperm are less frequently produced by affected males than X-bearing sperm, or that Y-bearing sperm are less capable of achieving fertilization. Numerous additional examples of sex-ratio have since been reported in other Drosophila species, but the identity of the causal genes has remained elusive. In this issue of PLoS Biology, Yun Tao and colleagues report the discovery and identity of an X-linked sex-ratio distorter from Drosophila simulans called Dox (Distorter on the X) [2]. In a second paper [3] they describe the identification of a dominant suppressor of Dox called Nmy (Not much yang). The close association of distorting and suppressing genes, though not appreciated by Gershenson, is key to understanding the genetic basis and evolutionary dynamics of sex-ratio systems. The long-term prospects of sexually reproducing populations that contain predominantly one sex are dire, and theory (commonly attributed to R.A. Fisher, but see [4] for an alternative attribution) suggests that an equal sex ratio is generally the most stable ratio over evolutionary time. Genes causing sex-ratio are therefore selfish genes, good at promoting an increase in their own frequency while potentially driving their host species …