Membrane exon sequences of the three Xenopus Ig classes explain the evolutionary origin of mammalian isotypes.
We have cloned and sequenced the genes corresponding to the membrane exons of the three immunoglobulin (Ig) heavy chain isotypes (mu, upsilon and chi) of Xenopus. Among membrane Ig (mIg) polypeptides, the transmembrane domain are the most highly conserved. The transmembrane and cytoplasmic domains of Xenopus mIgM are similar to the corresponding domains of all known vertebrate mIgM molecules, supporting the idea that amphibian mu gene is homologous, not just analogous, to the mu gene of higher vertebrates. The membrane forms of the two other Ig isotypes mIgX and mIgY exhibit the specific structure found in all Ig membrane exons, but are not homologous with any specific mammalian non-mu Ig isotype; they are most similar to Xenopus mIgM. Based on the conserved transmembrane domains of Xenopus mIgX, mIgY, we suggest that first the upsilon and later the chi genes arose by duplication from the original mu gene. The transmembrane and the 37-amino-acid-long cytoplasmic domains of Xenopus mIgY have conserved residues found in avian mIgY and mammalian mIgG and mIgE, suggesting that the modern isotypes might share a common ancestor with amphibian mIgY. However, while the sequence similarity between the membrane exons of avian mIgY and mammalian mIgG and IgE is striking, the overall similarity with Xenopus mIgY is very low. Thus, the genes giving rise to Xenopus mIgY and those eventually leading to avian mIgY and mammalian mIgG and mIgE must have diverged early in evolution, probably at the level of the primitive amphibians or before.
Mussmann
R
R
Basel Institute for Immunology, Switzerland.
Wilson
M
M
Marcuz
A
A
Courtet
M
M
Du Pasquier
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D005091:Exons / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000737:chemistry* / Q000145:classification / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014981:Xenopus
C016512:IgY; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell