12.18 : Dosage Compensation

In many organisms, females have two copies of an X chromosome, whereas males may have one X and one Y chromosome or one X chromosome. This means that the sexes differ in their dose of X chromosome genes.

Through a process called dosage compensation, an organism either upregulates or downregulates certain genes to equalize gene expression between sexes of the same species. This occurs via three mechanisms.

The first mechanism of dosage compensation can be found in humans. Initially, a female embryo has two active X chromosomes. The inactivation process begins at the blastocyst stage.

Both X chromosomes have an X chromosome inactivation center or X-I-C which has an X-I-S-T gene.

Blocking factors bind to the X-I-S-T gene of one X chromosome, and block its transcription.

The X-I-S-T gene of the other X chromosome produces an X chromosome-specific transcript, or X-I-S-T, which is an RNA.

This RNA wraps around the first X chromosome. Then, other proteins, called the X-I-S-T associated proteins, bind to the X-I-S-T RNA and begin to compact the chromosome, resulting in the formation of a Barr body.

All female somatic cells have one Barr body, whereas male somatic cells do not have any Barr bodies, as they have only one X chromosome.

The second mechanism of dosage compensation can be found in Drosophila.

Male Drosophila have a ratio of one X chromosome to two sets of autosomes. In females, it’s two to two.

 As a result, in developing males, two deadpan proteins block the binding of two sisterless proteins on the sex-lethal gene.

The sex-lethal gene becomes non-functional, which results in the translation of the male-specific lethal gene or M-S-L gene.

The M-S-L proteins bind to X-linked genes on the male X chromosome and increase their expression two-fold.

C. elegans follows the third mechanism. Here, a worm with two X chromosomes is a hermaphrodite, while a worm with one X chromosome is a male.

In the hermaphroditic worms, the dosage compensation complex, or D-C-C, binds to both X chromosomes and down-regulates the expression of genes on both X chromosomes.

In this system, half of the genes are active in one X chromosome, and the rest of the genes are active in the other X chromosome.