Domestic cats often resemble their larger, wilder counterparts—with black, striped, or tawny fur that presumably helps the big hunters blend into the landscape. For scientists, the genes involved in the evolution of cats' color patterns have been equally well-camouflaged. But a new study appearing online today in Science reveals a mutation shared by housecats and cheetahs, which may explain how the cat got its stripes—or in this case, its blotches.
The sharp, evenly spaced stripes of the tabby cat are among the most common of coat patterns. In some tabbies, however, the stripes look more like long, irregular swirls. Although fairly common in domestic cats, this pattern (called "blotched" by geneticists and cat fanciers) is unusual in the wild. In fact, cheetahs with the blotched pattern were initially thought to be a separate species—they were crowned with the name king cheetahs to distinguish them from the more common, spotted kind.
To pinpoint the gene responsible for the difference, an international team of researchers scanned the genomes of feral cats that had either stripes or blotches. Their search led to an unnamed gene about which little is known except that it produces an enzyme that cuts up nearby proteins. The researchers found that every blotched tabby had mutations in both copies of this gene, whereas every striped cat had at least one copy without the mutation. They then found the distinctive mutations in the same gene among DNA samples from a pedigreed family of king cheetahs, confirming their suspicions that mutations in the gene, which they dubbed Taqpep, turned ordinary stripes into the more regal blotches .
Further scrutiny of the cheetah skin made it clear that Taqpep didn't control the actual colors, because levels of the gene didn't change between dark and light areas. However, another gene, Edn3, was active at the base of the black hairs. Wondering if the two genes worked in tandem to produce stripes, the researchers studied housecat embryos at several stages of development. They found that the tabby pattern appears only after the hairs begin to grow at 7 weeks of gestation. Meanwhile, levels of Taqpep increase throughout gestation. The researchers propose that very early in development, Taqpep establishes a pattern of stripes or spots, which is then implemented by varying levels of Edn3 as the embryo grows. The role of Taqpep in setting the pattern early on also explains why the number of stripes or spots doesn't change as the cat ages (unlike in nonmammalian spotted animals such as salamanders and some fish).
"We knew the gene was out there, but we didn't know what it did. It's exciting to use the power of genetics to unravel these pathways," says co-author of the study Stephen O'Brien, a geneticist who was then at the National Laboratory for Cancer Research in Frederick, Maryland, but now heads the Theodosius Dobzhansky Center for Genome Informatics in St. Petersburg, Russia. 
"The possibility that Taqpep might be involved in pigment was totally off anyone's radar," says geneticist Sheila Schmutz of the University of Saskatchewan in Saskatoon, Canada. "Scientists who study color patterns now have a totally new gene with a well-defined function to work with."
O'Brien and his collaborators Gregory Barsh and Christopher Kaelin of the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama, wonder why cats have frequently spawned this plethora of color variation and why the blotch-producing Taqpep mutation didn't simply disappear after one or two generations in the wild. O'Brien is not convinced that protective coloration is the only survival advantage conferred by pigment-related genes like Taqpep. "Big predatory cats hunt their prey; camouflage may be helpful but isn't essential to survival," he notes. O'Brien predicts that color-producing genes will prove to play some other vital role—perhaps in resistance to disease. Taqpep, he says, belongs to a family of genes that are involved in immunity and produce receptors that are often co-opted by viruses seeking entry into a cell. A mutation in this gene may have helped some cats survive infection, he says.
Geneticist Elaine Ostrander of the National Human Genome Research Institute in Bethesda, Maryland, says that although many papers report a gene or two linked to a particular color, this work ties together several steps in a pattern-producing pathway. "It's an exciting missing piece of the puzzle," she says.