Figure 1. Variable gene content and dosage upregulation of the mammalian X chromosome.

a | Schematics of the human and mouse X chromosomes^1,11 are shown. The X conserved region (XCR; blue), which occupies the long arm and a small region of the short arm of the human X chromosome, and the X added region (XAR; green) are indicated. In mice, the XAR and XCR are rearranged. Many of the newly acquired ampliconic genes differ between humans (pink) and mice (orange). Note that the position of these regions does not necessarily represent the position of the ampliconic genes. b | The proto-X and proto-Y chromosomes originally had similar sizes, and their expression level was balanced with that of autosomal genes (which are present in two copies). After the Y chromosome degenerated, hemizygous X-linked genes became upregulated. There is evidence of at least two feedforward mechanisms, which are schematically represented by the different colour faucets for upregulation of X-linked genes in mammals, including increased transcription (yellow and green; large grey arrows) and extended RNA half-life (pink and purple; large black arrows). Additional feedback and buffering mechanisms that respond to any type of aneuploidy may also be implicated in X upregulation (blue; small black arrows). Genes that represent dosage-insensitive genes (black) would not be upregulated. Note that some genes may be regulated by more than one mechanism (red and orange). Part b is adapted from REF. 128.