Lamarck and Immunity : Somatic and Germline Evolution of Antibody Genes

摘要

Current work on the mechanism of hypermutation of somatically rearranged antibody variable (V) genes shows that the most likely mechanism involves both direct DNA modification (deamination of cytosines to uracils by AID deaminase) and strand nicking plus mRNA editing (deamination of adenosine to inosine via the ADAR1 deaminase) coupled to a reverse transcription process to fix RNA sequence modifications in V gene DNA – most likely involving the repair enzyme DNA polymerase eta (η) known to be an efficient reverse transcriptase in vitro. The DNA sequence patterns of families of similar germline V genes reveals that many features of somatically mutated and antigen-selected variable genes appear written into the germline V gene arrays of the immune system. Lamarckian gene feedback and cellular reverse transcription, coupled to Darwinian antigen binding selection of somatically mutated V genes, are concepts which appear necessary for a more complete understanding how the V gene complex has evolved. Antibody variable (V) genes of the immune system have therefore been used to test ideas on reverse transcriptase-coupled soma-to-germline feedback in a complex multicellular system. Such feedbackconstitutes a violation of Weismann's Barrier and thus support for some type of Lamarckian gene feedback operative during the evolution of the vertebrate immune system.