The impacts of cytoplasmic incompatibility factor (cifA and cifB) genetic variation on phenotypes

Abstract

Wolbachia are maternally transmitted, intracellular bacteria that can often selfishly spread through arthropod populations via cytoplasmic incompatibility (CI). CI manifests as embryonic death when males expressing prophage WO genes cifA and cifB mate with uninfected females or females harboring an incompatible Wolbachia strain. Females with a compatible cifA-expressing strain rescue CI. Thus, cif-mediated CI confers a relative fitness advantage to females transmitting Wolbachia. However, whether cif sequence variation underpins incompatibilities between Wolbachia strains and variation in CI penetrance remains unknown. Here, we engineer Drosophila melanogaster to transgenically express cognate and non-cognate cif homologs and assess their CI and rescue capability. Cognate expression revealed that cifA;B native to D. melanogaster causes strong CI, and cognate cifA;B homologs from two other Drosophila-associated Wolbachia cause weak transgenic CI, including the first demonstration of phylogenetic type 2 cifA;B CI. Intriguingly, non-cognate expression of cifA and cifB alleles from different strains revealed that cifA homologs generally contribute to strong transgenic CI and interchangeable rescue despite their evolutionary divergence, and cifB genetic divergence contributes to weak or no transgenic CI. Finally, we find that a type 1 cifA can rescue CI caused by a genetically divergent type 2 cifA;B in a manner consistent with unidirectional incompatibility. By genetically dissecting individual CI functions for type 1 and 2 cifA and cifB, this work illuminates new relationships between cif genotype and CI phenotype. We discuss the relevance of these findings to CI’s genetic basis, phenotypic variation patterns, and mechanism.

Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito vector

“…Other studies have shown infertility induced by cifB alone in D. melanogaster, induced by wPip's Type IV cifB homologue (also called cinB) and by the Type I cifB homologue from wRec, a CI-inducing strain found in Drosophila recens 47,48 . Neither study was able to demonstrate rescue of these effects and thus could not conclude that they were CI related 47,48 .…”

Mosquito Trilogy: Microbiota, Immunity and Pathogens, and Their Implications for the Control of Disease Transmission

“…Briefly, the molecular mechanism at the basis of CI has been recently elucidated: CI displays as embryonic death when a male expressing prophage WO genes cifA and cifB mate with an uninfected female or a female infected by an incompatible Wolbachia strain. In mosquito females harboring a compatible cifA-expressing strain rescue the embryonic development (LePage et al, 2017;Shropshire et al, 2021). Wolbachia has recently been detected in Ae.…”

Wolbachia cifBinduces cytoplasmic incompatibility in the malaria mosquito

“…In our view, our findings are supportive of a parsimonious toxin-antidote model where CifB is the toxin and CifA is the antidote. Lending support to this, other studies have shown some infertility induced by cifB alone in flies, with both w Pip’s Type IV cifB homolog (also called cinB) and w Rec’s Type I cifB gene, though neither study demonstrated rescue of these effects and thus could not conclude that they were CI related 28,29 . While it is plausible that in some systems CifA may stabilize or even potentiate CifB activity, our results rule out that CifA is always necessary for CI.…”