Recombination-based mechanisms for somatic hypermutation.

We review some experiments designed to test recombination-based mechanisms for somatic hypermutation in mice, particularly mechanisms involving templated mutation or gene conversion. As recombination and repair functions are highly conserved among prokaryotes and eukaryotes, pathways of mutation in microorganisms may prove relevant to the mechanism of somatic hypermutation. Escherichia coli initiates a recombination-based pathway of mutation in response to environmental stimuli, and this "adaptive" pathway of mutation has striking similarities with somatic hypermutation, as does a process of mutagenic repair that occurs at double-strand breaks in Saccharomyces cerevisiae. We present a model for recombination-based hypermutation of the immunoglobulin loci which could result in either templated or non-templated mutation.