Somatic hypermutation of TCR γ V genes in the sandbar shark

In a recent publication we demonstrated that somatic hypermutation occurs in the V region of the TCR gamma gene of the sandbar shark (Carcharhinus plumbous). We hypothesize that similar mechanisms are used to generate somatic mutations in both immunoglobulin and TCR gamma genes of the sharks. Two distinct patterns of mutation occur, single nucleotide mutations (point mutations) and mutations comprising 2-5 consecutive bases (tandem mutations). Our data indicates that point mutations occur by a mechanism similar to that of somatic hypermutation in immunoglobulin genes of mammals, whereas tandem mutations may be generated by an error-prone DNA polymerase with terminal deoxynucleotidyl transferase (TdT)-like activity. Shark hotspot motifs identical to those of higher vertebrates were identified. We confirm that, as in immunoglobulin of sharks and higher vertebrates, highly significant targeting of AID activity to the classical DGYW/WRCH motif occurs in somatic hypermutation of sandbar shark TCR gamma V genes. Our analysis suggests that the purpose of somatic mutations in shark TCR gamma V-regions is to generate a more diverse repertoire in gamma/delta receptors, rather than receptors with higher affinity. (C) 2011 Elsevier Ltd. All rights reserved.