The work of a scientific consortium lifts the veil on the malaria-carrying mosquito genome. Its high genetic polymorphism sheds light on the rapid development and propagation of insecticide resistance. It could also complicate genetic combat strategies.
Nothing is simple, and there are numerous complications when it comes to combating the mosquito responsible for transmitting malaria in tropical Africa. “Our discoveries regarding the remarkable genetic variability of Anopheles gambiae help to explain its high propensity to develop resistance to insecticides. They also suggest unexpected complexity in the development of genetic solutions,” states medical entomologist Carlo Costantini of IRD. He is the co-author of a major study on the subject, along with specialists united within a scientific consortium called “Anopheles gambiae 1000 genomes”.
Malaria is caused by the effect of a microscopic parasite, transmitted to humans by mosquito bites from the Anopheles genus. In 2016, this disease affected 216 million people in the world, and killed 445,000, 90% of whom were sub-Saharan children aged under 5 years. Until last year, these figures were constantly decreasing, particularly thanks to the generalisation of the use of insecticide impregnated mosquito nets around beds. However, this improvement is levelling off, probably because mosquitoes are becoming resistant to the products used. This is because combating the vectors using insecticides on sites where bites occur is the key strategy for preventing the disease.
“For the first time, we have sequenced and analysed the whole genome of 765 mosquitoes, Anopheles gambiae and Anopheles coluzzii from 15 localities across the whole African continent,” the researcher indicates. The result of the genome analysis on these insects is surprising to say the least. Their genetic polymorphism is twice as high as that of African fruit fly populations, and 10 times higher than that of Homo sapiens! Thus, these two-winged insects living in very varied environments (from the arid confines of the Sahel, to the equatorial rainforests) display many differences in the structure and arrangement of their genes.
Nevertheless, for certain genes, there is permeability between the various Anopheles populations. This allows characteristics to be passed between populations, when their members meet and reproduce. “This explains how mutations providing resistance to certain chemical molecules used to combat this vector can propagate in separate groups of insects, and rapidly from one side of the continent to the other,” indicates his colleague Diego Ayala. Combined with the lack of innovation in the domain of insecticides and the regulatory restrictions on their use, this problem particularly complicates the conventional fight against this vector. Certain scientists are therefore considering the development of approaches based on genomic bioengineering.
For example, this involves modifying mosquito genes (inserting or blocking them) to make these insects sterile or unable to transmit malaria parasites. By using genetic forcing methods, these modifications would then spread through vector populations or hinder their reproduction. “However, even in this area, our work shows a few nuances that could make this task more complicated than expected” he notes. “The genes and DNA sequences of interest in such a strategy display great polymorphism, so could rapidly lead to resistance, as already seen in experiments in cages with laboratory mosquitoes.” In the face of these constraints, the genetic battle is likely to target several genes of interest.