Early expression of two<Emphasis Type="Italic"> TdT</Emphasis> isoforms in the hematopoietic system of the Mexican axolotl |
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Authors: | Rachel?Golub Sébastien?André Alexandre?Hassanin Pierre?Affaticati Mani?Larijani Email author" target="_blank">Julien?S?FellahEmail author |
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Institution: | (1) Unité du Développement des Lymphocytes, CNRS URA 1961 Institut Pasteur, 25–28 rue du Docteur Roux, 75724 Paris Cedex 15, France;(2) Université Denis Diderot, Paris 7, 2 Place Jussieu, 75251 Paris Cedex 05, France;(3) Groupe dImmunologie Comparée, CNRS UMR 7622, Université Pierre et Marie Curie, 9 quai Saint-Bernard, boîte 24, 75252 Paris Cedex 05, France;(4) FRE 2695, Origine, Structure et Evolution de la Biodiversité, Département Systématique et Evolution, Muséum National dHistoire Naturelle, 55 rue Buffon, Case postale No.°51, 75005 Paris, France;(5) Medical Sciences Building, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5S 1A8, Canada |
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Abstract: | Nontemplate (N)-nucleotide addition by the terminal dideoxynucleotidyl transferase (TdT) at the junctions of rearranging V(D)J gene segments greatly contribute to antigen-receptor diversity. TdT has been identified in several vertebrate species, where it is highly conserved. We report here the isolation of two forms of TdT mRNA in an amphibian, the Mexican axolotl. The isoform TdT1 shares all of the conserved structural motifs required for TdT activity and displays an average of 50–58% similarity at the amino acid level with TdT of other species. The second axolotl TdT variant (TdT2) differs from TdT1 by a 57-amino acid deletion located between amino acids 165–222 of TdT1, including the first helix–hairpin–helix DNA-binding motif. During ontogeny, TdT products are first detected in the head of 6-week-old larvae and further in the head and trunk of 8-month-old larvae. These developmental stages correspond to the first detection of RAG1 and antigen-receptor (TCR and IgH) products in axolotl larvae. Our results suggest that in contrast to mammalian development, N diversity occurs early in axolotl development to diversify the primary repertoire. Phylogenetic analyses reveal that TdT and DNA polymerase (Pol ) genes are closely related, and that both enzymes were already present in the common ancestor of jawed vertebrates.This work is dedicated to the memory of Prof. Jacques CharlemagneThe sequences reported in this paper have been deposited in the GenBank database (accession numbers AF039209 and AY248700) |
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Keywords: | Amphibians Gene rearrangement Repertoire development Evolution |
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