PHYLOGENY OF IMMUNOGLOBULIN HEAVY-CHAIN ISOTYPES - STRUCTURE OF THE CONSTANT-REGION OF AMBYSTOMA-MEXICANUM UPSILON-CHAIN DEDUCED FROM CDNA SEQUENCE

An RNA polymerase chain reaction strategy was used to amplify and clon e a cDNA segment encoding for the complete constant part of the axolot l IgY heavy (Cupsilon) chain. Cupsilon is 433 amino acids long and org anized into four domains (Cupsilon1-Cupsilon4); each has the typical i nternal disulfide bond and invariant tryptophane residues. Axolotl Cup silon is most closely related to Xenopus Cupsilon (40% identical amino acid residues) and Cupsilon1 shares 46.4% amino acid residues among t hese species. The presence of additional cysteines in Cupsilon1 and Cu psilon2 domains is consistent with an additional intradomain S-S bond similar to that suggested for Xenopus Cupsilon and Cchi, and for the a vian Cupsilon and the human Cepsilon. Cupsilon4 ends with the Gly-Lys dipeptide characteristic of secreted mammalian Cgamma3, human Cepsilon 4, and avian and anuran Cupsilon4, and contains the consensus [G/GT(AA )] nucleotide splice signal sequence for joining Cupsilon4 to the tran smembrane region. These results are consistent with the hypothesis of an ancestral structural relationship between amphibian, avian upsilon chains, and mammalian epsilon chains. However, these molecules have di fferent biological properties: axolotl IgY is secretory Ig, anuran and avian IgY behave like mammalian IgG, and mammalian IgE is implicated in anaphylactic reactions.