FIG 5.

Models for cytoplasmic incompatibility (CI) caused by Wolbachia. (A) The 2-by-1 host modification (HM) model. Although the 2-by-1 model is strictly a genetic description, the most recently articulated version has been interpreted in the context of the HM mechanistic model shown here (20). CifA is regarded as the key CI-inducing factor that is responsible for modifications of sperm; CifB in this scheme has an undefined accessory role within the testes that is required for CI induction. In the fertilized egg, if CifA is secreted by infecting Wolbachia (blue ovals); it works in the opposite fashion to reverse the sperm modifications and rescues embryonic viability. Wolbachia is known not to be incorporated into mature sperm and is instead eliminated along with other organelles in the “waste bag” during spermiogenesis. There are multiple additional variants of the HM model that predate identification of the Cif proteins. (B) Toxin-antidote (TA) model. In this model, CifB is the fundamental CI-inducing factor and is postulated to be imported into the mature sperm (along with CifA); CifA may promote CifB levels or packaging into sperm or protect sperm precursors from CifB-induced toxicity. Upon fertilization, or possibly before, CifB enzymatic activity, either from the CidB deubiquitylase or CinB nuclease, alters the sperm-derived chromosomes in some way. CifB is proposed to be relatively long-lived, and CifA, the antidote that binds CifB, short-lived, so additional high-level expression of CifA in the egg is required to counter CifB activity.