EVOLUTION OF SOMATIC HYPERMUTATION AND GENE CONVERSION IN ADAPTIVE IMMUNITY

Examples of somatic hypermutation of antigen receptor genes can be see n in most lineages of vertebrates, including the cartilaginous fish. A nalysis of the phylogenetic data reveals that two distinctive features of the mechanism are shared by most species studied: the mutation hot spot sequence AGY, and a preponderance of point mutations. These data suggest that some of the components of the machinery are shared betwe en ectotherms and mammals. However, unique characters in particular sp ecies may have occurred by independent recruitment of novel factors on to the mechanism. A spotty phylogenetic distribution of gene conversio n has also been revealed and can be explained if the two mechanisms sh are some characteristics. Both mutation and conversion require transcr iption-related sequences and/or factors. We theorized that targeting t o V genes can be attained by a paused replication fork that has collid ed with a transcription complex stalled by a defective Ig transcriptio n activator; the paused replication fork results in recruitment of an error-prone translesion synthesis DNA polymerase (somatic hypermutatio n) or of DNA repair mechanisms with homologous recombination (gene con version). In addition, the pathway recruited in different species may be directed by the degree of homology among V genes.