Garfield has a dark secret. The cartoon cat is a genetic anomaly, not because of his insatiable lasagna cravings, but because of his coat color. Outside the world of the Sunday comics, orange and black cats are almost invariably female.

This truism is due to a curious biological phenomenon called X inactivation, which ensures that females of all species have only one active X chromosome in every cell. Early in development, when embryos have just few cells, one X chromosome is shut down or silenced in each cell. This chromosome remains inactive in all of that cell’s progeny throughout the life of the animal. In cats and many other species, the selection of the chromosome to be inactive is random; in some other species, the X chromosome inherited from the father is always chosen.

X inactivation is necessary to ensure that females, who have two X chromosomes, and males, who have only one, end up with roughly the same dosage of genes that occur on that chromosome.

The “orange or black fur” gene is on the X chromosome, so a female cat can have a calico coat with both colors if “orange” and “black” remain active in different cells, but because a male cat has just one X chromosome it can be only one of these colors.

Scientists have known about X inactivation for decades. Recently they learned that an RNA molecule called Xist is responsible. But it’s not been at clear exactly how Xist works to silence genes on the X chromosome.

Now researchers at the Stanford University School of Medicine have outlined the molecular steps of inactivation, showing that it occurs in an orderly and directed fashion as early embryonic cells begin to differentiate into more specialized tissues. They’ve identified more than 80 proteins in mouse cells that bind to Xist to help it do its job. They hope their findings will shed light on conditions in humans that are typically more severe in one gender than the other.