Good news! Can we eradicate bloodsuckers like mosquitos (without great harm)?
"New research into the genetics of Anopheles funestus (An. funestus), one of the most neglected but prolific malaria-transmitting mosquitoes in Africa, has revealed how this species is evolving in response to malaria control efforts. ...
The mosquito species An. funestus is one of the most widespread in Africa. Females of the species are highly anthropophilic, meaning they are attracted to humans as a source of blood, which they need to develop their eggs. They also have a significantly longer lifespan than other malaria-transmitting mosquito species. An. funestus is also extraordinarily adaptive. For example, in some areas, it has evolved from biting indoors in the evening to biting outdoors during the day, likely in response to the use of mosquito nets. Together, these characteristics make them formidable malaria transmitters in the part of the world where malaria remains most devastating. In 2023 the World Health Organisation African Region reported 569,000 malaria-related deaths. ...
To support this, mosquito biologists across Africa together with the team at the Sanger Institute collected and sequenced the whole genomes of 656 modern An. funestus mosquito specimens that were collected from 2014 to 2018.
They also sequenced 45 historic specimens from the Natural History Museum in London and the French National Research Institute for Sustainable Development (IRD) that were collected between 1927 and 1967 to understand the evolutionary patterns and changes in the species across 16 African countries during the last century.
The team found high levels of genetic variation in An. funestus across Africa and discovered that samples originating from equatorial countries shared many genetic similarities despite covering a 4,000-kilometre range. This suggests that they likely belong to one large, interconnected population. However, some samples from this region, such as those from North Ghana and South Benin, were isolated and genetically distinct from the interconnected population. This shows some populations mix widely, while others remain separate. Such population structure has important implications for mosquito control.
By looking at the DNA of the historic samples, the team was able to highlight the fast-evolving nature of An. funestus. One key mutation linked to insecticide resistance, which is widespread among the modern populations, was already present in the mosquitoes from the 1960s. However, other mutations that make mosquitoes resistant to insecticides were absent from the historic mosquitoes, suggesting that these became beneficial for the mosquitoes only later, as different insecticides were used in subsequent decades. ..."
From the editor's summary and abstract:
"Editor’s summary
Mosquitoes serve as vectors for diseases such as dengue and malaria; however, mosquito species are unequally represented in genetics studies. Two groups collected and analyzed extensive genomic data from mosquito disease vector species ... Crawford et al. sequenced 1206 individuals of the dengue and Zika vector Aedes aegypti and found that highly invasive populations split from earlier lineages during the Atlantic slave trade. They identified genomic regions potentially underlying human-specializing behavioral adaptations. Boddé et al. examined 656 modern Anopheles funestus individuals, as well as 45 museum specimens. They found multiple instances of insecticide-resistance variants in this malaria vector, although most of these weren’t shared with museum specimens collected as recently as 1967, suggesting rapid emergence. Such results will help to inform gene drive and insecticide efforts, as well as public health initiatives. ...
Structured Abstract
INTRODUCTION
The mosquito species Anopheles funestus is a major contributor to human malaria transmission across its vast sub-Saharan African range. Vector control of the other three major malaria-transmitting species in the Gambiae Complex has benefited from a deep understanding of genetic diversity, population structure, and the emergence and spread of insecticide resistance through the whole-genome sequencing of hundreds of individuals from many African countries. We completed whole-genome sequencing of 656 modern samples collected since 2014 and 45 historic samples collected between 1927 and 1967 to create a foundational understanding of genomic diversity in An. funestus across the continent.
RATIONALE
Since large scale deployment of insecticides began in the 1950s, An. funestus has rapidly evolved resistance throughout much of its range.
However, it is an open question whether resistance alleles have evolved independently in multiple locations, whether they are shared between different populations through gene flow, or whether resistant populations have entirely replaced historically susceptible populations.
A clearer genomic view on continental population structure is crucial for implementing strategic use of insecticides, taking into account the potential emergence and spread of insecticide resistance alleles. Additionally, with the implementation of gene drive release for vector control likely in the coming years, we need to be able to predict the spread of gene drive under different release scenarios, which is only possible if detailed knowledge of population connectivity across the continent, and how it varies along the genome, is in place.
RESULTS
We found that the 17 geographic regions from which our samples originated form six population clusters with varying degrees of genome-wide differentiation.
One of these populations, the Equatorial cohort, spans more than 4000 km and comprises individuals from seven countries. In close geographic proximity to this cohort, we found two genetically distinct ecotypes that appear to have a restricted range and distinct chromosomal karyotypes.
Using a windowed principal components analysis (PCA) approach, we explored structure across the genome. We used this approach to identify segregating inversions and classify every individual into its specific inversion karyotype. We also identified genomic regions that have exceptional levels of divergence in comparison to other collinear parts of the genome.
Some of these outlier regions are clearly driven by selection for insecticide resistance, as they contain loci with excessive haplotype sharing, often centered on genes known to play a role in insecticide resistance in many insect species. We show that the Gste2 resistance allele has at least two independent origins and that, despite reports of DDT resistance emerging in the 1950s, none of the historic samples in this study carry DDT resistance alleles found in modern-day populations.
CONCLUSION
Variable structure—such as that observed in this work, with some populations readily sharing alleles across the continent, and others clearly geographically proximal but genetically distinct—is a challenge for vector control. Even if the Gambiae Complex disappeared today, malaria would still rage through Africa until An. funestus is also effectively targeted. The greater understanding of the high levels of genetic diversity and the complex population structure of An. funestus presented in this study will underpin smarter surveillance and targeted vector control."
Genomic diversity of the African malaria vector Anopheles funestus (no public access)
Genomic diversity of the African malaria vector Anopheles funestus (preprint, open access)
Fig. 1 Population structure of 656 Anopheles funestus specimens collected across Africa.
No comments:
Post a Comment