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Terminal deoxynucleotidyl transferases from elasmobranchs reveal structural conservation within vertebrates

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Abstract

The DNA polymerase (pol) X family is an ancient group of enzymes that function in DNA replication and repair (pol β), translesion synthesis (pol λ and pol μ) and terminal addition of non-templated nucleotides. This latter terminal deoxynucleotidyl transferase (TdT) activity performs the unique function of providing diversity at coding joins of immunoglobulin and T-cell receptor genes. The first isolated full-length TdT genes from shark and skate are reported here. Comparisons with the three-dimensional structure of mouse TdT indicate structural similarity with elasmobranch orthologues that supports both a template-independent mode of replication and a lack of strong nucleotide bias. The vertebrate TdTs appear more closely related to pol μ and fungal polymerases than to pol λ and pol β. Thus, unlike other molecules of adaptive immunity, TdT is a member of an ancient gene family with a clear gene phylogeny and a high degree of similarity, which implies the existence of TdT ancestors in jawless fishes and invertebrates.

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Acknowledgements

This work was supported by grant 9605-ARG-0009 to SB from the North Carolina Biotechnology Center and grants R37 AI23338 to GWL and RR06603 to MF from the National Institutes of Health. The sequences reported here have been deposited in the GenBank database as accession numbers AY437557 (shark TdT) and AY437558 (skate TdT).

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  1. Moss Landing Marine Laboratories, 8272 Moss Landing Road, Moss Landing, CA 95039, USA

    Simona Bartl

  2. Department of Pediatrics, Children’s Research Institute, University of South Florida, St. Petersburg, FL 33701, USA

    Ann L. Miracle & Gary W. Litman

  3. Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201, USA

    Lynn L. Rumfelt, Evonne Mochon & Martin F. Flajnik

  4. Department of Biostatistics and Bioinformatics, Center for Bioinformatics and Computational Biology, IGSP, Duke University, Durham, NC 27708, USA

    Thomas B. Kepler

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  1. Simona Bartl
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Correspondence to Simona Bartl.

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Bartl, S., Miracle, A.L., Rumfelt, L.L. et al. Terminal deoxynucleotidyl transferases from elasmobranchs reveal structural conservation within vertebrates. Immunogenetics 55, 594–604 (2003). https://doi.org/10.1007/s00251-003-0608-3

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