The Toxin-Antidote Model of Cytoplasmic Incompatibility: Genetics and Evolutionary Implications

Abstract

Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of these and constitutes a promising weapon against vector-borne diseases. After decades of theoretical and experimental struggle, major recent advances have been made toward a molecular understanding of this phenomenon. As pieces of the puzzle come together, from yeast and Drosophila fly transgenesis to CI diversity patterns in natural mosquito populations, it becomes clearer than ever that the CI induction and rescue stem from a toxin-antidote (TA) system. Further, the tight association of the CI genes with prophages provides clues to the possible evolutionary origin of this phenomenon and the levels of selection at play.

Keywords: Wolbachia; cytoplasmic incompatibility; deubiquitylase; nuclease; selfish genetic elements; toxin–antidote systems.

Figure 1.. Cytoplasmic Incompatibility in Its Simplest Form.

Infectedfemalesarecompatiblewith both infected and uninfected males, whereas uninfected females produce viable offspring only if they mate with uninfected males. Abbreviation: w, Wolbachia-infected.

Figure 2.

In immature sperm, Wolbachia bacteria (pink) produce both a toxin (yellow particles) and its specific antidote (green particles). As Wolbachia are removed from maturing sperm into waste bags (W.b.), the antidote, presumably unstable, is lost faster than the toxin. Upon fertilization of an uninfected egg (left part), the toxin is thus present and active, impeding the paternal chromosomes through direct or indirect interactions with chromatin or DNA, which results in embryo death. In infected eggs, antidotes of maternal origin bind to the toxin and thus maintain embryo viability. Alternative cytoplasmic incompatibility (CI) mechanisms have been envisaged [21,22,82,83], but the model depicted here best accounts for all CI features [25], including its recently discovered genetic architecture [–29].

Figure 3.. A Nomenclature Proposal and Schematic View of Putative Cytoplasmic Incompatibility (CI) Operon Structures.

In this naming system, the cif (and Cif) terms designate CI genes (and proteins) in general, while genes from specific operon categories are named according to the enzymatic activity of the putative toxin [deubiquity-lase (DUB), nuclease (Nuc), or both]. The first and second genes within each operon are denoted A and B, respectively, and the Wolbachia strain is indicated as a superscript when relevant. The structure of several CI operons is shown to illustrate this system; active-site residues are labeled. Abbreviation: ORF, open reading frame.