title: Evolution of coordinated mutagenesis and somatic hypermutation in VH5.
abstract: The VH5 human antibody gene was analyzed using a computer program (mfg) which simulates transcription, to better understand transcription-driven mutagenesis events that occur during "phase 1" of somatic hypermutation. Results show that the great majority of mutations in the non-transcribed strand occur within loops of two predicted high-stability stem-loop structures, termed SLSs 14.9 and 13.9. In fact, 89% of the 2505 mutations reported are within the encoded complementarity-determining region (CDR) and occur in loops of these high-stability structures. In vitro studies were also done and verified the existence of SLS 14.9. Following the formation of SLSs 14.9 and 13.9, a sustained period of transcriptional activity occurs within a window size of 60-70 nucleotides. During this period, the stability of these two SLSs does not change, and may provide the substrate for base exchanges and mutagenesis. The data suggest that many mutable bases are exposed simultaneously at pause sites, allowing for coordinated mutagenesis.
authors: Division of Biological Sciences, The University of Montana, Missoula, MT 59812, USA. barbara.wright@mso.umt.edu
authors: Barbara E
authors: BE
authors: Wright
authors: Karen H
authors: KH
authors: Schmidt
authors: Aaron T
authors: AT
authors: Hunt
authors: Dennis K
authors: DK
authors: Reschke
authors: Michael F
authors: MF
authors: Minnick
mesh_terms: D001324:Autoantigens / Q000276:immunology; D001483:Base Sequence; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000276:immunology; D009690:Nucleic Acid Conformation; D027041:Somatic Hypermutation, Immunoglobulin; D014158:Transcription, Genetic
chemical_list: D001324:Autoantigens; C063762:CDR1 protein, human; C095184:CDR2 protein, human; D007143:Immunoglobulin Heavy Chains; D009419:Nerve Tissue Proteins