ArticleImmunogenetics2026
Reconstructed amphibian heavy-chain constant regions support a mosaic origin of IgXA with IgY-like CH1-CH2, an intermediate CH3, and an IgM-like CH4.
Article in Immunogenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The evolutionary relationship between amphibian IgM, IgY, and IgX/A-like antibodies has remained difficult to resolve, largely because repetitive heavy-chain loci are often incompletely or inconsistently annotated. In this study, I re-analyzed reconstructed four-domain heavy-chain constant regions from amphibian loci to test whether the evolution of IgXA is better explained by uniform divergence or by a mosaic history involving partial exon replacement. The reconstructed dataset comprised 86 complete antibodies from 29 species (29 IgM, 33 IgY, and 24 IgXA). Exact nucleotide matching against the reconstructed exon set yielded 79 antibodies, allowing the identification of 21 strictly microsyntenic species-level IgM/IgY/IgXA trios for recombination analyses. Domain alignments, Poisson-corrected amino-acid distances, and UMAP embeddings revealed a clear structural transition: IgXA clustered closer to IgY in CH1 and CH2, remained nearly intermediate in CH3, and shifted decisively toward IgM in CH4. Mean inter-class distances (IgY-IgXA vs. IgM-IgXA) reflected this pattern: 0.964 vs. 1.275 in CH1, 1.254 vs. 1.477 in CH2, 1.242 vs. 1.248 in CH3, and 1.220 vs. 0.962 in CH4. Within-species trio comparisons reinforced this polarity: 16 of 21 trios displayed an IgY-like CH1-CH2, 16 exhibited an IgM-like CH4, and 12 combined both features. Furthermore, GARD detected recombination breakpoints close to the CH3/CH4 boundary in 6 of the 21 trios, including three cases within 30 nucleotides of the exon junction. Maximum-likelihood domain trees confirmed that the strongest IgXA-IgM sister relationship occurred in CH4, where the largest relevant clade showed 91.7/89.0 SH-aLRT/UFBoot support. Together, these reconstructed sequence data support a mosaic origin for amphibian IgXA, most parsimoniously explained by partial exon shuffling or replacement within a conserved constant-region genomic block.
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