dosagecompensation

Dosage compensation is a set of molecular mechanisms that balance gene expression from sex chromosomes between individuals of different sexes. In species with heterogametic sexes (for example, XY males and XX females), the number of X chromosomes differs between sexes, which could otherwise cause over- or underexpression of X-linked genes.

In mammals, dosage compensation is achieved by silencing one X chromosome in female cells. The process is initiated by transcription of the XIST gene on the future inactive X, which coats that chromosome and recruits chromatin-modifying complexes. The result is transcriptional silencing of most X-linked genes and the formation of a Barr body, though a subset of genes escapes inactivation and remains expressed from both X chromosomes. The end effect is roughly equal X-linked gene expression between males and females.

In Drosophila melanogaster and many other insects, males upregulate expression from their single X chromosome to match the female twofold dose. This is accomplished by the Male-Specific Lethal (MSL) complex, which binds the male X and promotes transcription, including through histone modification such as acetylation of histone H4 on lysine 16 (H4K16ac). The result is balanced overall expression between the sexes.

In Caenorhabditis elegans, XX hermaphrodites downregulate transcription from both X chromosomes by about half, while XO males maintain one active X. A dosage compensation complex coordinates chromosome-wide repression to yield comparable X-linked expression between the sexes.

Across species, the degree and mechanism of dosage compensation vary, with incomplete or gene-by-gene compensation observed in some lineages, such as certain birds, where Z-linked gene expression is not fully equalized.