Inverse complementary homologues of short cysteine signatures

Inversions of short genomic sequences may play a central role in the genera tion of protein complexity. We report here the existence of an heterogeneou s group of proteins (the trefoil precursors MUC-1 and MUA-1, six preproendo thelins, and five classes of zinc finger knot proteins) having both cystein e signatures (<(Cs)over bar>) and their inverse complementary sequences (<( Cs)over bar>) in the same polypeptide chain. We have also found cases in wh ich the ( <(Cs)over bar>) of a given signature is not present in the same protein, but elsewhere. TGEKPYK, a cysteine-free motif of the human transcr iption factor, Krab, coexists with its inverse complementary sequence in 31 proteins; the inverse complementary alone is present in a great number of proteins. Our findings suggest that short DNA inversions are a widespread f eature of the genome. (C) 2000 Academie des sciences/Editions scientifiques et medicales Elsevier SAS.