Loss of splice consensus signal is responsible for the removal of the entire C(H)1 domain of the functional camel IGG2A heavy-chain antibodies.
The molecular basis for the absence of the C(H)1 domain in naturally occurring heavy-chain antibodies of the camelids was assessed by determining the entire Camelus dromedarius gamma2a heavy-chain constant gene. The organization of the camel gamma2a constant heavy-chain gene obtained from a liver genomic library appears to be typical of all other mammalian gamma genes sequenced to date. It contains the switch, CH1, hinge, CH2, CH3, M1 and M2 exons. In contrast to the case in mouse and human heavy chain diseases, the camel gamma2a gene shows no major structural defect, and its equivalent CHI exon is intact. However, sequence analysis has revealed that the splicing site, immediately after the CH1 exon, is defective due to point mutations, especially the G(+1) to A(+1) transversion seems to be detrimental. It is concluded that the loss of the splice consensus signal is responsible for the removal of the entire CH1 domain in camel gamma2a heavy-chain immunoglobulins. Additionally, a closer analysis of the hinge exon suggests the possible involvement of transposons in the genetic variation of mammalian Cgamma hinges.
Nguyen
V K
VK
Department of Ultrastructure, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Belgium. nguykhon@vub.ac.be
Hamers
R
R
Wyns
L
L
Muyldermans
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002162:Camelus / Q000235:genetics* / Q000276:immunology*; D002417:Cattle; D002462:Cell Membrane / Q000276:immunology; D016384:Consensus Sequence; D003593:Cytoplasm / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005803:Genes, Immunoglobulin; D052058:Hinge Exons; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000737:chemistry / Q000235:genetics; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000235:genetics; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007134:Immunoglobulin Switch Region; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D012326:RNA Splicing / Q000235:genetics; D011817:Rabbits; D051381:Rats; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D018076:DNA, Complementary; D007127:Immunoglobulin Constant Regions; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains