Heavy chain V region diversity in the duck-billed platypus (Ornithorhynchus anatinus): long and highly variable complementarity-determining region 3 compensates for limited germline diversity.
In this work, to study the emergence of the H chain V region repertoire during mammalian evolution, we present an analysis of 25 independent H chain V regions from a monotreme, the Australian duck-billed platypus, Ornithorhynchus anatinus. All the sequences analyzed were found to form a single branch within the clan III of mammalian V region sequences in a distance tree. However, compared with a classical V gene family this branch was more diversified in sequence. Sequence analysis indicates that the apparent lack of diversity in germline V segments is well compensated for by relatively long and highly diversified D and N nucleotides. In addition, extensive sequence variation was observed in the framework region 3. Furthermore, at least five and possibly seven different J segments seem to be actively used in recombination. Interestingly, internal cysteine bridges in the complementarity-determining region (CDR)3 loop, or between the CDR2 and CDR3 loops, are found in approximately 36% of the platypus V(H) sequences. Such cysteine bridges have also been observed in cow, camel, and shark. Internal cysteine bridges may play a role in stabilizing long and diversified CDR3 and thereby have a role in increasing the affinity of the Ab-Ag interaction.
Johansson
Jeannette
J
Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, SE751 24 Uppsala, Sweden.
Aveskogh
Maria
M
Munday
Barry
B
Hellman
Lars
L
D000595:Amino Acid Sequence; D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D022801:Complementarity Determining Regions / Q000032:analysis / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis; D018095:Germ-Line Mutation / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000032:analysis* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000032:analysis* / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D010987:Platypus / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment / Q000379:methods
D022801:Complementarity Determining Regions; D018076:DNA, Complementary; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region