Multiple IgH Isotypes Including IgD, Subclasses of IgM, and IgY Are Expressed in the Common Ancestors of Modern Birds

J Immunol. 2016 Jun 15;196(12):5138-47. doi: 10.4049/jimmunol.1600307. Epub 2016 May 16.


Although evolutionarily just as ancient as IgM, it has been thought for many years that IgD is not present in birds. Based on the recently sequenced genomes of 48 bird species as well as high-throughput transcriptome sequencing of immune-related tissues, we demonstrate in this work that the ostrich (Struthio camelus) possesses a functional δ gene that encodes a membrane-bound IgD H chain with seven CH domains. Furthermore, δ sequences were clearly identified in many other bird species, demonstrating that the δ gene is widely distributed among birds and is only absent in certain bird species. We also show that the ostrich possesses two μ genes (μ1, μ2) and two υ genes (υ1, υ2), in addition to the δ and α genes. Phylogenetic analyses suggest that subclass diversification of both the μ and υ genes occurred during the early stages of bird evolution, after their divergence from nonavian reptiles. Although the positions of the two υ genes are unknown, physical mapping showed that the remaining genes are organized in the order μ1-δ-α-μ2, with the α gene being inverted relative to the others. Together with previous studies, our data suggest that birds and nonavian reptile species most likely shared a common ancestral IgH gene locus containing a δ gene and an inverted α gene. The δ gene was then evolutionarily lost in selected birds, whereas the α gene lost in selected nonavian reptiles. The data obtained in this study provide significant insights into the understanding of IgH gene evolution in tetrapods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution
  • Birds / genetics
  • Birds / immunology
  • Evolution, Molecular*
  • Gene Expression Profiling
  • Genes, Immunoglobulin*
  • High-Throughput Nucleotide Sequencing
  • Immunoglobulin D / genetics*
  • Immunoglobulin D / immunology
  • Immunoglobulin M / classification
  • Immunoglobulin M / genetics*
  • Immunoglobulin delta-Chains / genetics
  • Immunoglobulins / classification
  • Immunoglobulins / genetics*
  • Phylogeny
  • Reptiles / genetics
  • Reptiles / immunology
  • Sequence Alignment
  • Struthioniformes / genetics
  • Struthioniformes / immunology*


  • IgY
  • Immunoglobulin D
  • Immunoglobulin M
  • Immunoglobulin delta-Chains
  • Immunoglobulins