Models and Nomenclature for Cytoplasmic Incompatibility: Caution over Premature Conclusions – A Response to Beckmann et al.

The proposed TA model [ 4 Beckmann J.F. et al. The toxin–antidote model of cytoplasmic incompatibility: genetics and evolutionary implications. Trends Genet. 2019; 35 : 175-185 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ] assumes that male-derived CifB (the presumed toxin) is transferred to the host embryo during fertilization and that its associated defects are rescued upon binding to embryo-derived CifA (the presumed antidote). Although CifA and CifB bind to each other in vitro [ 3 Shropshire J.D. et al. One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogaster. Proc. Natl. Acad. Sci. U. S. A. 2018; 115 : 4987-4991 Crossref PubMed Scopus (0) Google Scholar ], there is no evidence for transfer of CifB to the embryo. In fact, there is evidence to the contrary that was mentioned by the authors. Mass spectrometry and SDS-PAGE analyses indicate that CifA, but not CifB, is present in the spermatheca of females mated to infected males [ 5 Beckmann J.F. Fallon A.M. Detection of the Wolbachia protein WPIP0282 in mosquito spermathecae: implications for cytoplasmic incompatibility. Insect Biochem. Mol. Biol. 2013; 43 : 867-878 Crossref PubMed Scopus (35) Google Scholar ]. There are numerous technical explanations for why CifB is absent – for example, CifB protein expression levels may be below the threshold of detection – but the current evidence is consistent with a model wherein CifA, but not CifB, reaches the female reproductive tract. Therefore, it cannot be assumed that CifB from the male directly interacts with CifA in the embryo. For this reason the essential premise of the TA model is unfounded. One of several alternative hypotheses is that, instead of CifB transferring with the sperm, a host product modified by CifA and/or CifB leads to CI induction, and the host modification is then reversed by CifA in the embryo [ 3 Shropshire J.D. et al. One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogaster. Proc. Natl. Acad. Sci. U. S. A. 2018; 115 : 4987-4991 Crossref PubMed Scopus (0) Google Scholar ]. It is notable that, if supported, this model and others ( Figure 1B) would contradict the proposed TA model