The source of self: genetic parasites and the origin of adaptive immunity.

Stable colonization of the host by viruses (genetic parasites) can alter the systems of host identity and provide immunity against related viruses. To attain the needed stability, some viruses of prokaryotes (P1 phage) use a strategy called an addiction module. The linked protective and destructive gene functions of an addiction module insures both virus persistence but will also destroy cells that interrupt this module and thereby prevent infection by competitors. Previously, I have generalized this concept to also include persistent and lytic states of virus infection, which can be considered as a virus addiction module. Such states often involve defective viruses. In this report, I examine the origin of the adaptive immune system from the perspective of a virus addiction module. The likely role of both endogenous and exogenous retroviruses, DNA viruses, and their defective elements is considered in the origin of all the basal components of adaptive immunity (T-cell receptor, RAG-mediated gene rearrangement, clonal lymphocyte proliferation, antigen surface presentation, apoptosis, and education of immune cells). It is concluded that colonization by viruses and their defectives provides a more coherent explanation for the origin of adaptive immunity.