A ‘sex-distorting’ approach to control malaria-spreading mosquitoes, first proposed in theory sixty years ago, my be closer to reality. A new study in the journal Nature Communications from an international team led by researchers in Imperial College London, describes use of an endonuclease from slime mould to selectively shred the X chromosome of the malaria mosquito vector Anopheles gambiae. This has a two-fold effect as it results in males having almost exclusively male offspring, leading to reductions in population over time and also reduces malaria spread as only female mosquitoes bite humans and transmit malaria.
Malaria remains a serious public health issue, most notably in sub-Saharan Africa. The disease kills hundreds of thousands of people every year. In mosquitoes, like humans, normal sperm contains 50% X and 50% Y chromosomes. The current study exploited the fact that the endonuclease I-Ppol selectively targets cutting sites located exclusively on the X chromosome of Anopheles gambiae. The research team used a combination of protein engineering and molecular genetics to produce male mosquitoes in which the I-Ppol was turned on only during spermatogenesis. Therefore, these males produced almost no X chromosome-containing sperm as the X chromosomes were shredded by the endonuclease, and hence very few female offspring. Importantly, the modification was heritable so that many of the male offspring of the original males also produced few female offspring.
The results were striking. In five test cages originally containing 50 males and 50 females each, introduction of 150 sex-distorter males resulted in a major reduction in females over 4 generations and in complete loss of the population after another 2 generations in 4 out of 5 cages. The results are promising and are unlikely to have a serious impact on the surrounding ecosystem as, for example, it specifically targets the malarial mosquito unlike pesticides which are more indiscriminate. However, the system is some years away from deployment in the field.
Commentators have welcomed the study but point out that targeting the Y chromosome would represent a better long-term strategy as the modified males would pass the change on to all of their male offspring and there would be less dilution of the effect than would be likely with the system in the current study, which would probably need ‘topping up’ over time. The authors of the current paper agree with this analysis and in fact have been working on gene insertions in the mosquito Y chromosome. Thus the future looks promising for harnessing of sex-distorting strategies to control spread of malaria.
Sources
Galizi, R., Doyle, L. A., Menichelli, M., Bernardini, F., Deredec, A., Burt, A., Stoddard, B. L., Windbichler, N., and Crisanti, A. (2014). A synthetic sex ratio distortion system for the control of the human malaria mosquito. Nature Communications, Vol. 5 (10 June 2014), doi:10.1038/ncomms4977
BBC News; available from http://www.bbc.com/news/science-environment-27765974 [Accessed 13 June 2014]
Malaria remains a serious public health issue, most notably in sub-Saharan Africa. The disease kills hundreds of thousands of people every year. In mosquitoes, like humans, normal sperm contains 50% X and 50% Y chromosomes. The current study exploited the fact that the endonuclease I-Ppol selectively targets cutting sites located exclusively on the X chromosome of Anopheles gambiae. The research team used a combination of protein engineering and molecular genetics to produce male mosquitoes in which the I-Ppol was turned on only during spermatogenesis. Therefore, these males produced almost no X chromosome-containing sperm as the X chromosomes were shredded by the endonuclease, and hence very few female offspring. Importantly, the modification was heritable so that many of the male offspring of the original males also produced few female offspring.
The results were striking. In five test cages originally containing 50 males and 50 females each, introduction of 150 sex-distorter males resulted in a major reduction in females over 4 generations and in complete loss of the population after another 2 generations in 4 out of 5 cages. The results are promising and are unlikely to have a serious impact on the surrounding ecosystem as, for example, it specifically targets the malarial mosquito unlike pesticides which are more indiscriminate. However, the system is some years away from deployment in the field.
Commentators have welcomed the study but point out that targeting the Y chromosome would represent a better long-term strategy as the modified males would pass the change on to all of their male offspring and there would be less dilution of the effect than would be likely with the system in the current study, which would probably need ‘topping up’ over time. The authors of the current paper agree with this analysis and in fact have been working on gene insertions in the mosquito Y chromosome. Thus the future looks promising for harnessing of sex-distorting strategies to control spread of malaria.
Sources
Galizi, R., Doyle, L. A., Menichelli, M., Bernardini, F., Deredec, A., Burt, A., Stoddard, B. L., Windbichler, N., and Crisanti, A. (2014). A synthetic sex ratio distortion system for the control of the human malaria mosquito. Nature Communications, Vol. 5 (10 June 2014), doi:10.1038/ncomms4977
BBC News; available from http://www.bbc.com/news/science-environment-27765974 [Accessed 13 June 2014]
