EVIDENCE OF THE COEVOLUTION OF A SNAKE TOXIN AND ITS ENDOGENOUS ANTITOXIN CLONING, SEQUENCE AND EXPRESSION OF A SERUM-ALBUMIN CDNA OF THE CHINESE COBRA

A full-length cDNA of the serum albumin (CSA) of the cobra (Naja naja kaouthia) was cloned from a lambda gt 11 library. It encodes a mature protein of 614 amino-acid residues homologous to the precursor of mamm alian serum albumins. The 1 degrees and 2 degrees structures of the CS A resemble those of the human variety. The putative toxin binding site s are mainly located in the subdomains IIA and IIIA. The relation betw een structural homology and function of the serum albumins (SA) is dis cussed. An analysis of their evolutionary tree revealed that anti-toxi city arose by < 90 amino-acid exchanges. The rate of substitution is m uch higher in the SA than in cytochrome C, which probably reflects the difference in evolutionary driving forces. The evolutionary period of the SA (6.7 +/- 0.1 M.Y.) significantly exceeds that of hemoglobin (5 .8 M.Y.). Eight tripeptides in the nicotinic acetylcholine receptor (A CR), all flanking the putative toxin binding site, are also found in t he CSA where they join to form 1 octa-, 1 penta- and 4 tripeptides, th us indicating the concerted evolution of two functionally linked prote ins: toxin and antitoxin (CSA).