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Evolutionary dynamics of the immunoglobulin heavy chain variable region genes in vertebrates

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Abstract

Immunoglobulin heavy chains are polypeptides encoded by four genes: variable (IGHV), joining (IGHJ), diversity (IGHD), and constant (IGHC) region genes. The number of IGHV genes varies from species to species. To understand the evolution of the IGHV multigene family, we identified and analyzed the IGHV sequences from 16 vertebrate species. The results show that the numbers of functional and nonfunctional IGHV genes among different species are positively correlated. The number of IGHV genes is relatively stable in teleosts, but the intragenomic sequence variation is generally higher in teleosts than in tetrapods. The IGHV genes in tetrapods can be classified into three phylogenetic clans (I, II, and III). The clan III and/or II genes are relatively abundant, whereas clan I genes exist in small numbers or are absent in most species. The genomic organization of clan I, II, and III IGHV genes varies considerably among species, but the entire IGHV locus seems to be conserved in the subtelomeric or near-centromeric region of chromosome. The presence or absence of specific IGHV clan members and the lineage-specific expansion and contraction of IGHV genes indicate that the IGHV locus continues to evolve in a species-specific manner. Our results suggest that the evolution of IGHV multigene family is more complex than previously thought and that several factors may act synergistically for the development of antibody repertoire.

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Acknowledgments

We thank Nikolas Nikolaidis, Dimitra Chalkia, Zhenguo Lin, and Hiroki Goto for their valuable comments and suggestions. This work was supported by NIH grant GM020293-35 to MN.

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Authors and Affiliations

  1. Department of Biology, Institute of Molecular Evolutionary Genetics, Pennsylvania State University, University Park, PA, 16802, USA

    Sabyasachi Das, Masafumi Nozawa, Jan Klein & Masatoshi Nei

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  1. Sabyasachi Das
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  2. Masafumi Nozawa
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  3. Jan Klein
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  4. Masatoshi Nei
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Correspondence to Sabyasachi Das.

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Supplemental Figure 1

Flowchart for identification of IGHV genes in the vertebrate genomes (GIF 38.4 kb)

High resolution image file (TIF 11.1 mb)

Supplemental Table 1

List of IGHV genes in 16 vertebrate species (DOC 1.86 mb)

Supplemental Table 2

Flanking repeat elements of IGHV genes used for identifying orthologous and paralogous genes between humans and chimpanzees. See footnote for detailed information(DOC 237 kb)

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Das, S., Nozawa, M., Klein, J. et al. Evolutionary dynamics of the immunoglobulin heavy chain variable region genes in vertebrates. Immunogenetics 60, 47–55 (2008). https://doi.org/10.1007/s00251-007-0270-2

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