The reverse transcriptase model of somatic hypermutation.

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Conclusionsƒ

We have shown that many of the current experimental Findings on somatic hypermutation can be interpreted under the RT model. The basic principles can also be applied to gene conversion processes, for example in chicken Ig loci, hitherto thought of as being mechanistically unrelated to somatic hypermutation (Blanden & Steele 1998). Furthermore, the paradoxical appearance of the somatic hypermutation signature in the germline unrearranged IgV segment repertoire (Blanden et al. 1998)is consistent with
soma-to-germlinefeedback of mutated sequences from B cells over evolutionary time. This concept has been strengthened by reports of uptake and integration by mammalian sperm of DNA and RNA, and RT activity in sperm which provide a mechanism for movement of somatic gene sequences to the germline (Giordano et al. 2000; Zoraqi & Spadafora 1997; Perry et al. 1999), e.g. from apoptotic memory lymphocytes that have migrated to germ tissues (Rothen£uh 1995).