Cytoplasmic Incompatibility: An Autocidal Mechanism for Controlling the Mosquito Inhabitants


Cytoplasmic incompatibility, which leads to non-reciprocal fertility, is a naturally occurring phenomenon, but remains largely unexplored for the control of insect vector populations. This mechanism deserves priority for mosquito control and disease transmission reduction, is non-insecticidal, and is easier to operate with minimal investment.

Cytoplasmic incompatibility in mosquitoes

Together with other insect populations of economic importance, the phenomenon of cytoplasmic incompatibility (CI) has been extensively documented in natural mosquito populations of a particular species as well as in closely related groups of species. CI restricts gene flow and leads to postzygotic reproductive isolation and speciation events.

Origin of the cytoplasmic incompatibility

The phenomenon of cytoplasmic incompatibility was ascribed to the presence of intracellular, obligate, maternally inherited rickettsia-like symbiotic microorganisms of the genus Wolbachia. If mosquito larvae are made free of this infection (aposymbiotic) by treatment with tetracycline, bidirectional fertility is restored at reciprocal crosses.

The underlying mechanism of CI, however, remains unexplained for a number of reasons: (i) inconsistent results for mismatched observed crossbreeding relationships, (ii) inconsistent separation of cytoplasmic properties and crossbreeding types with common maternal ancestors, (iii) mode of action of these pathogens who have favourited incapacitating sperm / stop karyogamy.

Wolbachia strains are known to be very diverse, which in turn appeared to explain the variation in levels of cytoplasmic incompatibility observed in natural mosquito populations.

In general, female mosquitoes harboring Wolbachia strains show compatibility with males infected with a similar type versus both sexes infected with different strains, resulting in sterility. Interestingly, uninfected men are compatible with infected women, regardless of strain / mixed staining (superinfection). Conversely, uninfected women are incompatible with infected men.

Genetics of cytoplasmic incompatibility: empirical evidence

Based on cross-breeding schemes, the unidirectional fertility observed in intraspecific (between populations) and interspecific (between species) crosses has been attributed to the nuclear-independent maternal line known as “cytoplasmic incompatibility”.

For example, crosses with Aedes malayensis females x Ae. Alcasidi males were fertile while cross-breeding with Ae. alcasidi women x ae. Malayensis males (despite fertilization) were sterile (all eggs laid were unsafe).

The hybrid males derived from the cross (Ae. Malayensis females x Ae. Alcasidi males) also gave no viable offspring when crossed back to Ae. Alcasidi females, therefore incompatibility showed a strictly maternal mode of inheritance, which is shown as follows:

Female Male
Ae. Malayensis (w +) Yes. Alcasidi (w-) F1 (Ae. Malayensis x Ae. Alcasidi)
Ae. Malayensis (w +) + + +
Yes. Alcasidi (w-) – – + – –
F1 (Ae. Malayensis x Ae. Alcasidi) * + + +

* In the hybrid cross, the first named species in brackets was used as the female parent.

(+) = Compatibility, (-) = incompatibility, (w +) = Wolbachia present, (w-) = Wolbachia missing. In this case, while Ae. Malayensis is known to be home to Wolbachia (w +), Ae. Alcasidi is free from this infection (w-).

Note that incompatibility occurs when males infected with Wolbachia are crossed with uninfected women.

In this case, a sequential backcrossing scheme aimed at genomic replacement also did not change the compatibility status of the first female parent used in the hybrid cross, proving the hypothesis that the phenomenon of CI is a core independent, stable and permanent trait.

In addition, it has been shown in Culex pipiens mosquitoes that CI persists throughout the life of the mosquito regardless of the age of the parents concerned.

A similar phenomenon has been observed in many other closely related species of the Aedes (Stegomyia) scutellaris group, vectors of filariasis in the South Pacific islands.

Cytoplasmic incompatibility: an effective barrier to genetic flow / introgression

This naturally occurring phenomenon of CI has played a critical role in evolution and speciation, restricting gene flow and introgression between inbred populations of a particular species, as well as between species and hybrids. Additionally, it could work in a gene propulsion system to replace the mosquito genome as well as reduce population size or modulate the age structure of the population to reduce disease transmission.

Accordingly, it has been postulated that Wolbachia could be used (i) as a tool to drive desirable genotypes into arthropod populations, and (ii) to directly suppress or modify natural insect vector populations.

Impact on population control

The success story of the eradication of Culex pipiens fatigans (a vector of Bancroftian filariasis) by CI in a defined geographic area has been documented. The scheme involved a mass release of bidirectionally incompatible males of the target species, which as such are harmless in that they do not require blood meal.

Aedes albopictus female mosquito. (Source: Centers for Disease Control and Prevention Public Health Image Library,

Control of the insect vector population by CI has obvious advantages in that it is cost effective, eliminates the need for insecticidal use and thus prevents insecticide resistance from emerging. In addition, the existing ethical guidelines and practices for a mass release program, without applying a multitude of rules and regulations, will be sufficient to get approval quickly.

If cytoplasmic incompatible men were used to control Aedes albopictus (the Asian tiger mosquito), there is an additional benefit, as infected women have a reproductive benefit compared to uninfected women due to both CI and a fitness increase associated with Wolbachia infection have host longevity, egg hatching rates, and fertility.

One size doesn’t fit everyone: a good time to attack again

If in a given region the Wolbachia strains circulating and exhibiting CI are different, the situation offers the opportunity to use them to control indigenous vector populations. Thus, there is the possibility of integrating this incompatible insect technology (IIT) with other control methods such as sterile insect technology (SIT) and the use of larvicides to effectively treat insect vector populations.

Population cage experiments with CI strains have proven to be a gala success. This technology holds great promise for large-scale releases of commercial insect vector control, which could prove to be a novel environmentally friendly tool.

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