A new model and method for understanding Wolbachia-induced cytoplasmic incompatibility

Abstract

Wolbachia are intracellular bacteria transmitted almost exclusively vertically through eggs. In response to this mode of transmission, Wolbachia strategically manipulate their insect hosts' reproduction. In the most common manipulation type, cytoplasmic incompatibility, infected males can only mate with infected females, but infected females can mate with all males. The mechanism of cytoplasmic incompatibility is unknown; theoretical and empirical findings need to converge to broaden our understanding of this phenomenon. For this purpose, two prominent models have been proposed: the mistiming-model and the lock-key-model. The former states that Wolbachia manipulate sperm of infected males to induce a fatal delay of the male pronucleus during the first embryonic division, but that the bacteria can compensate the delay by slowing down mitosis in fertilized eggs. The latter states that Wolbachia deposit damaging "locks" on sperm DNA of infected males, but can also provide matching "keys" in infected eggs to undo the damage. The lock-key-model, however, needs to assume a large number of locks and keys to explain all existing incompatibility patterns. The mistiming-model requires fewer assumptions but has been contradicted by empirical results. We therefore expand the mistiming-model by one quantitative dimension to create the new, so-called goalkeeper-model. Using a method based on formal logic, we show that both lock-key- and goalkeeper-model are consistent with existing data. Compared to the lock-key-model, however, the goalkeeper-model assumes only two factors and provides an idea of the evolutionary emergence of cytoplasmic incompatibility. Available cytological evidence suggests that the hypothesized second factor of the goalkeeper-model may indeed exist. Finally, we suggest empirical tests that would allow to distinguish between the models. Generalizing our results might prove interesting for the study of the mechanism and evolution of other host-parasite interactions.

Figure 1. How bidirectionally and unidirectionally incompatible Wolbachia strains are represented in the lock-key-model.

(A) strains and are bidirectionally incompatible: Neither nor has the key to each other's lock. (B) and are unidirectionally incompatible: has the key to 's lock, but does not have the key to 's lock.

Figure 2. How the goalkeeper model's two quantitative factors produce the known CI patterns.

Females and males can either be uninfected or infected by Wolbachia. Two factors, and , are involved in the generation of CI. Wolbachia contribute to factor and to factor in equal amounts during modification in males and rescue in females (dashed arrows). Hosts contribute the net host contribution to factor and to factor in females only. Rescue occurs within the red areas, either due to hosts only (top row) or in combination with Wolbachia (bottom row). The blue asterisk shows the modification by Wolbachia (right column). CI occurs only if this blue asterisk does not lie within the rescue area because this implies that at least one of the factors or is produced at greater quantity in males than in females (top right).

Figure 3. The compatibility relationships of six studied Wolbachia strains.

These relationships were used to study whether the goalkeeper-model and the lock-key-model are able to reproduce empirical data. Threshold for CI: corrected CI level of 20%. The host species is D. simulans in all studies. References: (1) , (2) , (3) , (4) .

Figure 4. Explanation of the compatiblity relationship using the goalkeeper-model.

The points represent the contribution by the corresponding Wolbachia strain to the two mod factors ( and ). The black arrow represents the host contribution to rescue. The contribution of a strain to the two resc factors equals its own contribution plus the net host contribution. When both resc factors exceed both mod factors in quantity, rescue is successful. Thus wTei with the help of the net host contribution rescues wRi (indicated by wRi being within the dotted frame). In contrast, wRi can rescue wMel but not wTei (indicated by wMel but not wTei being within the dashed frame).