

Figure 1: Calico cat. The patchy distribution of color on calico cats results from the random inactivation of one X chromosome in females. Ksmith4f via Wikimedia Commons.

Unlike the gene-poor Y chromosome, the X chromosome contains over 1,000 genes that are essential for proper development and cell viability. However, females carry two copies of the X chromosome, resulting in a potentially toxic double dose of X-linked genes. To correct this imbalance, mammalian females have evolved a unique mechanism of dosage compensation distinct from that used by organisms such as flies and worms. In particular, by way of the process called X-chromosome inactivation (XCI), female mammals transcriptionally silence one of their two Xs in a complex and highly coordinated manner (Lyon, 1961). The inactivated X chromosome then condenses into a compact structure called a Barr body, and it is stably maintained in a silent state (Boumil & Lee, 2001).

A prime example of X inactivation is in the coat-color patterning of tortoiseshell or calico cats (Figure 1). In cats, the fur pigmentation gene is X-linked, and depending on which copy of the X chromosome each cell chooses to leave active, either an orange or black coat color results. X inactivation only occurs in cells with multiple X chromosomes, which explains why almost all calico cats are female.

X inactivation exists in two different forms: random and imprinted. Although both forms utilize the same RNAs and silencing enzymes, they differ in terms of their developmental timing and mechanism of action.