Replacing Wild-Type Mosquitoes with Genetically Modified Mosquitoes

HONORS 220B

Paper 2

October 25, 2017

Genetically modified, malaria parasite-resistant mosquitoes have altered mating preferences

compared to wild-type mosquitoes, allowing them to easily pass down their resistance genes from

generation to generation.
 Thus far, attempts to prevent the spread of malaria have involved bed nets, anti-malarial drugs,

and insecticides, among others. The cost of these interventions, however, has prevented them from

achieving their maximum effectiveness. Researchers have begun considering an alternative approach

to combat malaria, which is to replace natural mosquito populations with genetically modified (GM)

mosquitoes resistant to the malaria parasite Plasmodium. How can GM mosquitoes successfully

introduce and increase Plasmodium resistance in natural mosquito populations? Pike et al. (2017)

hypothesized that changing the mating preferences of GM mosquitoes would increase the overall

Plasmodium resistance in a mosquito population. If mating is in favor of GM mosquitoes, allowing

more offspring to have the resistant genes, then mosquito populations should become increasingly

resistant over time.

The researchers first created five strains of GM, Plasmodium-resistant mosquitoes by

increasing the expression of immune genes in the mosquitoes midguts. They then compared the strains

fitness to that of wild-type mosquitoes and created a mosquito population that was half GM and half

wild-type. Every generation, they measured the proportion of GM mosquitoes in the population and

plotted the proportions on a line graph. To assess GM mosquitoes mating preferences, they drew upon

previous research showing that fruit flies mating preferences change based on the composition of their

microbiota. Since increased immune gene expression in the midgut would affect GM mosquitoes

microbiota, Pike et al. tested whether or not GM mosquitoes had different mating preferences than

wild-type mosquitoes. They measured how often GM mosquitoes preferred either wild-type or GM

mates, did the same with wild-type mosquitoes, and summarized their results in bar graphs. If their

hypothesis was correct, they would see mating preferences that favor GM mosquitoes, which would

result in a higher proportion of GM mosquitoes in the end population (Figure 1). If their hypothesis

was incorrect, they would see that mating preferences that favor GM mosquitoes would not increase

the proportion of GM mosquitoes in the population (Figure 1).

 The five strains of GM mosquitoes had similar fitness compared to each other and to the wild-

type mosquitoes, as they had similar lifespans and laid the same number of eggs (Figure 2). As for

mating preferences, GM males preferred to mate with wild-type females and wild-type males preferred

to mate with GM females (Figure 3). Lastly, GM mosquitoes comprised 90% of the population after

just one generation, and maintained this proportion for the next nine generations (Figure 4).

The results were consistent with Pike et al.s hypothesis. From the results, one can infer that

GM mosquitoes increased immune resistance altered their microbiota, which in turn changed their

mating preferences. Ultimately, the shift in mating preferences allowed GM mosquitoes to dominate

the population over time. One of the biggest unknowns is whether or not GM mosquitoes would

maintain the same mating preferences in nature instead of in a laboratory setting. A next step could be

to repeat the experiment in a more natural setting, observing if GM mosquitoes mating preferences

change and if they are still effective at replacing wild-type mosquitoes in a population.

While using GM mosquitoes to propagate Plasmodium resistance into natural mosquito

populations may be effective in reducing malarial infections, releasing them into the wild is too risky

at this moment. So far, there is little research on how GM mosquitoes behave in the wild, which means

that they may pose risks in natural settings that researchers are not yet aware of. For instance, GM

mosquitoes may become vectors for other diseases, which they could easily transmit to humans.

Furthermore, Plasmodia may evolve to overcome GM mosquitoes increased immune function, which

would not only reignite the spread of malaria but also make malaria much tougher to eradicate. It may

be ethically questionable to not use a potentially very effective intervention, but it is just as

questionable to start using the intervention without a full risk assessment. Researchers should be in no

hurry to release GM mosquitoes into malaria-afflicted regions; they should take as much time as they

need in showing that the short- and long-term benefits of using GM mosquitoes far outweigh the costs.
 Figures

If hypothesis is correct: If hypothesis is incorrect:

1
1
strong 0.8
0.8 preference strong
for GM 0.6 preference

% GM
0.6 for GM
% GM

0.4 weak/no
0.4
weak/no preference
preference 0.2 for GM
0.2 for GM

0 0
1 6 1 6
Generation Generations

Figure 1 Predictions under the hypothesis and the null hypothesis. If the hypothesis is correct, mating
preferences that favor GM mosquitoes should result in GM mosquitoes making up most of the
population. If the hypothesis is incorrect, mating preferences that favor GM mosquitoes would not
increase the proportion of GM mosquitoes in the population.

Figure 2 Fitness of GM mosquitoes compared to fitness of wild-type mosquitoes. (A) GM mosquitoes

have a similar lifespan to both each other and wild-type mosquitoes. (B) GM females and wild-type
females lay the same number of eggs, on average. Source: Pike et al. (2017)
Figure 3 Mating preferences of GM and wild-type males. (A) GM (CpRel215) males mated more with
wild-type females than GM females. (B) Wild-type males mated more with GM females than wild-
type females. Source: Pike et al. (2017)

Figure 4 Proportion of GM mosquitoes in the population over ten generations. After one generation,
the proportion of GM mosquitoes was 90%, which stayed relatively constant over the next few
generations. Source: Pike et al. (2017)
 Citations

Pike, A., Dong, Y., Dizaji, N. B., Gacita, A., Mongodin, E. F., & Dimopoulos, G. (2017). Changes in

the microbiota cause genetically modified Anopheles to spread in a population. Science,

357(6358), 1396-1399. doi:10.1126/science.aak9691