Recombination, truncation and horizontal transfer shape the diversity of cytoplasmic incompatibility patterns

Wolbachia are endosymbiotic bacteria inducing various reproductive manipulations of which cytoplasmic incompatibility (CI) is the most common. CI 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 CI causal genes, cidA and cidB, with polymorphism located in the CidA-CidB interaction regions. We previously showed correlations between the identity of gene variants and CI patterns. However, these correlations were limited to specific crosses, and it is still unknown whether cid gene polymorphism in males' and females' Wolbachia can explain and predict the wide range of crossing types observed in C. 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 outside the interface regions and strongly correlated with CI 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 CI. The identity of the sole full-length cidB variant seems to dictate CI 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 CI induction.