Recombination, truncation and horizontal transfer shape the diversity of <i>Wolbachia-</i>induced cytoplasmic incompatibility patterns

Wolbachia are endosymbiotic bacteria inducing various reproductive manipulations of which cytoplasmic incompatibility is the most common. Cytoplasmic incompatibility leads to reduced embryo viability in crosses between males carrying Wolbachia and uninfected females or those carrying an incompatible symbiont strain. In the mosquito Culex pipiens, the Wolbachia wPip causes highly complex crossing patterns. This complexity is linked to the amplification and diversification of the cytoplasmic incompatibility causal genes, cidA and cidB, with polymorphism located in the CidA-CidB interaction regions. We previously showed that some compatibility patterns correlated with the presence or absence of specific cid variants. It is still unknown, however, whether cid gene polymorphism alone is sufficient to explain the diversity of crossing patterns observed in Cx. pipiens. Taking advantage of a new method enabling full-gene acquisition, we sequenced complete cid repertoires from 45 wPip strains collected worldwide. We demonstrated that the extensive diversity of cid genes arises from recombination and horizontal transfers. We uncovered further cidB polymorphism located outside the interface regions and strongly correlated with cytoplasmic incompatibility patterns. Most importantly, we showed that in every wPip genome, all but one cidB variant are truncated. Truncated cidBs located in palindromes are partially or completely deprived of their deubiquitinase domain, crucial for cytoplasmic incompatibility. The identity of the sole full-length cidB variant seems to dictate cytoplasmic incompatibility patterns, irrespective of the truncated cidBs present. Truncated CidBs exhibit reduced toxicity and stability in Drosophila cells, which potentially hinders their loading into sperm, essential for cytoplasmic incompatibility induction.