Calico CAT


The calico cat (also known as tortoiseshell-and-white) holds an exalted position in the (short) history of the field of X-chromosome inactivation.  The coat color of the calico cat was instrumental in the formulation of the X-chromosome inactivation hypothesis by Mary Lyon 50 years ago (Lyon, 1961.pdf).  Calico cats are almost exclusively females and comprise of two colors of fur on an otherwise white background.  Lyon proposed that this coat color pattern arises due to inactivation of one or the other of the two X-chromosomes.  In the orange patches in the calico cat shown above, it is the X-chromosome that harbors the brown allele that has been inactivated.  In brown patches, it is the X that has the orange allele that is inactivated. 

(To answer a question about origins of the white coat color: it is due to an autosomal gene that affects migration of melanocytes - pigment-producing cells; the slower the migration, the more the fur is white.  Calico cats typically have lots of white fur but rather discrete patches of brown and orange colored fur.  Cats with very little white fur and which display a brindled pattern with a more intimate mixture of brown and orange lie at the other end of the spectrum and are referred to as tortoiseshell cats - close cousins of calico cats.)

The second key point - arguably the more important one - predicted by Lyon’s hypothesis is that X-inactivation is a very stable phenomenon and that the discreteness of the patches is due to clonal expansion of precursor cells that had earlier inactivated one or the X-chromosome.  The implication being that once inactivated, the same X-chromosome is stably maintained as such through multiple rounds of cell division.