Molly Vernersson (a), (b), Maria Aveskogh (a), (b) and Lars Hellman (a), (b)
Developmental & Comparative Immunology, 2004 28: 61-75
*1 The sequence presented is submitted to GenBank, accession number AY099258.
In continuation of our evolutionary studies of immunoglobulin (Ig) expression, we present here the cloning of IgE from a monotreme, the short-beaked echidna (Tachyglossus aculeatus). Including echidna IgE, 15 chain sequences have been isolated and each of the three mammalian lineages (placentals, marsupials and monotremes) is now represented by at least two sequences. Phylogenetic analyses based on all available chains and a selection of other mammalian Ig isotypes (IgM, IgA and IgG) were generated using three different algorithms. The resulting trees strongly support the Theria hypothesis, which states that the monotreme lineage was the first of the three extant mammalian lineages to appear in evolution. Furthermore, to increase our understanding of IgE we have done a detailed comparative analysis, with focus on primary structure, potential N-glycosylation, charge distribution and conservation of residues in the putative receptor-binding site. The overall structure of IgE, i.e. four constant domains and the positions of putative disulfide-bridge formations, are conserved, as is an N-glycosylation site in the third constant domain. An increased homology was observed in the putative receptor-binding site, which suggests an important function for the IgE/FcRI interaction. IgE has been found exclusively in mammals, but it is present in all extant mammalian lineages. This, together with the overall conservation of structure, indicates that IgE appeared as a separate isotype early in mammalian evolution and that structural maintenance may have a selective advantage.
Author Keywords: Immunoglobulins; IgE; chain; Mammals; Monotreme; Evolution; FcRI interaction; N-glycosylation Abbreviations: Ig, immunoglobulin; bp, base pair; pI, isoelectric point; NJ, neighbor joining; ML, maximum likelihood; MP, maximum parsimony
Corresponding author. Address: Department of Cell and Molecular Biology, Immunology Programme-Biomedical Center, University of Uppsala, P.O. Box 596, Uppsala S-751 24, Sweden. Tel.: +46-18-471-4532; fax: +46-18-471-44347
(a) Department of Cell and Molecular Biology, Immunology Programme-Biomedical Center, University of Uppsala, P.O. Box 596, Uppsala S-751 24, Sweden
(b) Resistentia Pharmaceuticals AB, P.O. Box 853, Uppsala S-753 23, Sweden