Color markings among felid species display both a remarkable diversity and a
common underlying periodicity. A similar range of patterns within domestic cats suggests a
conserved mechanism whose appearance can be altered by selection. We identify the gene
responsible for tabby pattern variation in domestic cats as Transmembrane aminopeptidase Q
(Taqpep), which encodes a membrane-bound metalloprotease. Analyzing 31 other felid species
we identify Taqpep as the cause of the rare king cheetah phenotype, in which spots coalesce into
blotches and stripes. Histologic, genomic expression, and transgenic mouse studies indicate that
paracrine expression of Endothelin3 (Edn3) coordinates localized color differences. We propose
a two-stage model in which Taqpep helps to establish a periodic pre-pattern during skin
development that is later implemented by differential expression of Edn3.
