Somatic hypermutation of TCR γ V genes in the sandbar shark

Abstract

In a recent publication we demonstrated that somatic hypermutation occurs in the V region of the TCR γ gene of the sandbar shark (Carcharhinus plumbeus). We hypothesize that similar mechanisms are used to generate somatic mutations in both immunoglobulin and TCR γ 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 γ V genes. Our analysis suggests that the purpose of somatic mutations in shark TCR γ V-regions is to generate a more diverse repertoire in γ/δ receptors, rather than receptors with higher affinity.