The Genetics of Calico Cats

In mammals, sex is determined by two sex chromosomes, known as the X and the Y chromosomes. Genes located on either the X or the Y chromosome are known as "sex-linked" genes. Genes on any chromosomes other than the X or Y are known as autosomal genes.

The Karyotype: A Visualization of the Chromosomes

Normal female mammals have two X chromosomes. Normal males have one X and one Y chromosome. This can be seen in this human male karyotype:

The X and Y chromosomes appear at the bottom right corner of the image. If this were a female, the two sex chromosomes would both be relatively larger X chromosomes. As you can see, compared to the X chromosome, the Y chromosome is small and carries fewer genes.

The exact genes carried on the X chromosome varies among species. In humans, for example, the gene coding for normal clotting factors and the gene coding for normal cone photoreceptor pigment are located on the X chromosome. Abnormal mutant forms of these genes can result in hemophilia (a potentially fatal disorder in which the blood fails to clot) in the former case, and red-green color blindness in the latter.

Cats: One X-linked Gene with Two Alleles for Coat Color

In cats, one of several genes controlling fur color is located on the X chromosome. The gene has two versions, or alleles. One form of the gene codes for orange fur (XB), and the other form codes for black fur (Xb). While it's difficult to say which allele is dominant and which is recessive, since only one is ever expressed (see below), let's say, for the sake of argument, that orange is dominant to black. Ordinarily, this would mean that an animal inheriting one copy of each gene (genotype XBXb) should have orange fur. Surprisingly, a female cat heterozygous at that locus (XBXb) will not be orange. Instead, her coat will be a patchwork of orange and black, a condition known as tortoiseshell. Why is she not just orange?

Female Genotypes

There are three possible female genotypes for this locus:

Male Genotypes

Males, having only one X chromosome, carry only one allele for the orange vs. black fur color trait. The Y does not carry this allele at all, being much smaller and having fewer loci than the X chromosome. The condition of carrying only one allele for a particular trait is known as hemizygosity (from the Greek hemi, meaning "half" and "zygote", referring to the fertilized egg).

There are two possible (normal) male genotypes:

or

Expression of Coat Color in Males

Male color expression is straightforward. Because only one allele exists for the gene in each cell, it will be expressed. And all males have only B or only b. There are no heterozygotes, because the Y does not carry the allele.

Expression of Coat Color in Females

In females, the situation is more complicated because of an interesting process that prevents the female from expressing double the amount of X-linked gene products as the male, who has only one copy of each X-linked gene.

At a certain point in the embryonic development of every female mammal (including cats), one of the two X chromosomes in each cell inactivates by supercoiling into a structure known as a Barr Body. This irreversible process is known as Lyonization; it leaves only ONE active X chromosome in each cell of the female embryo. Only the alleles on the active (uncoiled) X chromosome are expressed.

Lyonization is random in each cell: there's no way to predict which of the two X chromosomes will become inactivated. Hence, any given cell of a heterozygous female could end up as either of the following:


In the diagram on the left, the orange allele is inactivated. In the one on the right, the black allele is inactivated.

A heterozygous cat will be a patchwork of these two types of cells. Lyonization takes place relatively early in development, when the cat is still a blastula, and all the cells descended from a blastomere with a particular X chromosome inactivated as a Barr Body will also have the same Barr Body inactivated. That means that all the skin tissues that arise from a cell like the left one will express black fur, and all the skin tissue that arise from a cell like the right one will express orange fur.
Hence:

This is known as mosaic expression.

Here's an overview:

This is why calico cats are almost invariably female.

Can Male Cats Ever be Tortoiseshell?

In rare cases, a male cat can inherit two X chromosomes in addition to his Y chromosome (Klinefelter Syndrome). If this happens, each cell in the male embryo will undergo Lyonization, just as a female's would. If the two X chromosomes do not carry the same allele (i.e., the cat's genotype is XBXbY), then the male will express calico coloration, just as a female would. But he'll also have the disadvantages that go along with Klinefelter Syndrome.

Real, Live Cats

A tortoiseshell cat is one with black and orange patches. She is heterozygous at the X-linked coat color locus.

A calico cat is a tortoiseshell expressing an additional genetic condition known as piebalding. A piebald animal has patches of white (i.e., unpigmented) skin/fur. This is controlled by a different locus (S) than the black/orange fur colors.

The patches may be relatively large, or rather small and interwoven:

Larger patches may be caused by: