Balancing sex chromosome expression and satisfying the sexes

Abstract

Equalizing sex chromosome expression between the sexes when they have largely differing gene content appears to be necessary, and across species, is accomplished in a variety of ways. Even in birds, where the process is less than complete, a mechanism to reduce the difference in gene dose between the sexes exists. In early development, while the dosage difference is unregulated and still in flux, it is frequently exploited by sex determination mechanisms. The Drosophila female sex determination process is one clear example, determining the sexes based on X chromosome dose. Recent data show that in Drosophila, the female sex not only reads this gene balance difference, but at the same time usurps the moment. Taking advantage of the transient default state of male dosage compensation, the sex determination master-switch Sex-lethal which resides on the X, has its expression levels enhanced before it works to correct the gene imbalance. Intriguingly, key developmental genes which could create developmental havoc if their levels were unbalanced show more exquisite regulation, suggesting nature distinguishes them and ensures their expression is kept in the desirable range.

Figure 1. Status of X chromosome transcription in early Drosophila embryos. Female with two Xs shown at the top, male with single X below, with the chromosome size depicting relative intensity of transcribed genes. As SXL levels rise in females, it begins to reduce X chromosome transcript elevation by repressing MSL-2 expression as well by directly dosage compensating genes, like run. Male state is default and continues uninterrupted.