TY - JOUR
T1 - Somatic hypermutation of TCR γ V genes in the sandbar shark
AU - Chen, Hao
AU - Bernstein, Harris
AU - Ranganathan, Parvathi
AU - Schluter, Samuel F.
N1 - Funding Information:
This work was supported by Grant MCB- 0621853 from the National Science Foundation to SFS. We thank Igor Rogozin for analyzing mutation profiles with the CLUSTERM program.
PY - 2012/5
Y1 - 2012/5
N2 - 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 D. GYW/WR. CH 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.
AB - 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 D. GYW/WR. CH 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.
KW - Adaptive immune system
KW - Evolution
KW - Shark
KW - Somatic hypermutation
KW - T cell receptor
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U2 - 10.1016/j.dci.2011.08.018
DO - 10.1016/j.dci.2011.08.018
M3 - Article
C2 - 21925537
AN - SCOPUS:84862794919
SN - 0145-305X
VL - 37
SP - 176
EP - 183
JO - Developmental and Comparative Immunology
JF - Developmental and Comparative Immunology
IS - 1
ER -