Identification of IgF, a hinge-region-containing Ig class, and IgD inXenopus tropicalis

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Abstract
Only three Ig isotypes, IgM, IgX, and IgY, were previously known in amphibians. Here, we describe a heavy-chain isotype in Xenopus tropicalis, IgF (encoded by Cφ), with only two constant region domains. IgF is similar to amphibian IgY in sequence, but the gene contains a hinge exon, making it the earliest example, in evolution, of an Ig isotype with a separately encoded genetic hinge. We also characterized a gene for the heavy chain of IgD, located immediately 3′ of Cμ, that shares features with the Cδ gene in fish and mammals. The latter gene contains eight constant-region-encoding exons and, unlike the chimeric splicing of μCH1 onto the IgD heavy chain in teleost fish, it is expressed as a unique IgD heavy chain. The IgH locus of X. tropicalis shows a 5′ VH-DH-JH-Cμ-Cδ-Cχ-Cυ-Cφ 3′ organization, suggesting that the mammalian and amphibian Ig heavy-chain loci share a common ancestor.