The recent sequencing of the complete genome of the fruit fly Drosophila me
lanogaster has yielded about 30% of the predicted genes with no obvious cou
nterparts in other organisms. These rapidly evolving genes remain largely u
nexplored. Here, we present evidence for a striking variability in an impor
tant Drosophila cell cycle regulator encoded by the gene roughex (rux) in c
losely related fly species. The unusual level of Rux protein variability in
dicates that there are very low overall constraints on amino acid substitut
ions. Despite the lack of sequence similarity, certain common features, inc
luding the presence of a C-terminal nuclear localization signal and a funct
ionally important N-terminal RXL cyclin-binding motif, exist between Rux an
d cyclin-dependent kinase inhibitors of the Cip/Kip family. These results i
ndicate that even some genes involved in key regulatory processes in eukary
otes evolve at extremely high rates.