The Chromosomal Cause of the Calico-Colored Cat

Have you ever been told that almost all calico-coloured cats are female? Have you ever wondered how such a thing could be true? The answer to this lies within their DNA; with a phenomenon found in all female mammals called X-chromosome inactivation.

The sex-determining system of all mammals dictates that females have two X-chromosomes and males have one X- and one Y-chromosome. While the Y-chromosome contains few genes, the X-chromosome contains over one-thousand 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 disparity, mammalian females have evolved a unique mechanism of dosage compensation called X-chromosome inactivation.

At the sixty-four-cell stage of embryonic development, this process randomly silences, or inactivates, one of the two X-chromosomes. The choice of which X is inactivated in a particular cell is unaffected by the choice of that cell’s neighbours. The silenced chromosome then condenses and is stably maintained in this inactive state throughout all future cell divisions in the life of that individual.

A prime example of X-chromosome inactivation can be found in the calico coat colour patterning exhibited in some cats. In these cats, the fur pigmentation gene is X-linked; one X-chromosome encodes an orange coat colour and the other gives a black or tabby. Depending on which X-chromosome each cell chooses to leave active, either an orange or a black coat colour results and the cat’s fur becomes a mosaic of patches. Only cells with multiple X-chromosomes can undergo X-chromosome inactivation, which explains why almost all calico-coloured cats are female. The coat colour is a result of the sex of the cat, not the other way around.

The white patches are often seen in the coat of calico cats, in addition to the orange and black patches, are a result of an autosomal influence on the final coat markings. An autosome is any of the numbered chromosomes, as opposed to the sex chromosomes. For example, humans have twenty-two pairs of autosomes and one pair of sex chromosomes (the X-chromosome and the Y-chromosome). A calico-coloured cat that has white on it is simply a calico-coloured cat expressing an additional genetic condition dictated by its autosomes known as piebalding, which is caused by unpigmented skin and fur.

The exception to this rule is observed, albeit very rarely, in male cats whose chromosome makeup contains an XXY-complement. The occurrence of this complement allows X-chromosome inactivation to take place in these male cats giving them the familiar calico-coloured coat. Unfortunately, sterility and other conditions are also very common traits in cats with this XXY-complement.

The study of X-chromosome inactivation may also provide insight into cancer biology, as two active X’s have been found in many human breast and ovarian tumours. The role this plays in animals, however, has not yet been studied.


Ahn, J., & Lee, J. (2008). X chromosome: X inactivation. Nature Education, 1(1), 24.

Centerwall, W. R., & Benirschke, K. (1975). An animal model for the XXY Klinefelter’s syndrome in man: tortoiseshell and calico male cats. American journal of veterinary research, 36(9), 1275-1280.

Gartler, S. M., & Goldman, M. A. (2005). X‐chromosome Inactivation. eLS.

Lyon, M. F. (1999). X-chromosome inactivation. Current Biology, 9(7), R235-R237.

Morey, C., & Avner, P. (2011). The demoiselle of X-inactivation: 50 years old and as trendy and mesmerising as ever. PLoS Genet, 7(7), e1002212.

Osgood, M. P. (1994). X-Chromosome Inactivation: The Case of the Calico Cat1. Ann Arbor MI, 48109, 1048.

Written by Leigh Holizki, Technologist Assistant



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Last updated: December 16, 2020

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