Genomic diversity of the African malaria vector Anopheles funestus.
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| Title: | Genomic diversity of the African malaria vector Anopheles funestus. |
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| Authors: | Boddé, Marilou, Nwezeobi, Joachim, Korlević, Petra, Makunin, Alex, Akone-Ella, Ousman, Barasa, Sonia, Gadji, Mahamat, Hart, Lee, Kaindoa, Emmanuel W., Love, Katie, Lucas, Eric R., Lujumba, Ibra, Máquina, Mara, Nagi, Sanjay C., Odero, Joel O., Polo, Brian, Sangbakembi, Claire, Dadzie, Samuel, Koekemoer, Lizette L., Kwiatkowski, Dominic |
| Source: | Science. 9/18/2025, Vol. 389 Issue 6766, p1-14. 14p. |
| Subjects: | Anopheles funestus, Genetic variation, Insecticide resistance, Insect genetics, Genomes |
| Abstract: | Anopheles funestus s.s. is a major human malaria vector across Africa. To study its evolution, especially under vector control pressure, we sequenced 656 modern specimens (collected 2014 to 2018) and 45 historic specimens (collected 1927 to 1967) from 16 African countries. Despite high genetic diversity, the species shows stable but considerable continental population structure. Although one population showed little differentiation over a century and 4000 kilometers, nearby, we found two genetically distinct ecotypes. Vector control has resulted in strong signals of selection, with some resistance alleles shared across populations through gene flow and others arising independently. Fortunately, we found that a promising gene drive target in Anopheles gambiae is highly conserved in An. funestus. These insights will enable more strategic insecticide usage and gene drive deployment, supporting malaria elimination. 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 (see the Perspective by Carter). 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. —Corinne Simonti 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. Continental population structure among 656 modern An. funestus specimens.: PCA, fixation index (FST), and a windowed PCA approach reveal how population structure varies across the continent and along the genome. The windowed PCA shows distinct patterns for segregating inversions (including double recombinants) and loci under positive selection. Insecticide resistance mutations were found in selective sweeps on different haplotypic backgrounds, suggesting multiple independent origins, but most resistance mutations were not observed in 45 historic specimens. SNP, single-nucleotide polymorphism; L119F, Leu119Phe mutation. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Anopheles funestus s.s. is a major human malaria vector across Africa. To study its evolution, especially under vector control pressure, we sequenced 656 modern specimens (collected 2014 to 2018) and 45 historic specimens (collected 1927 to 1967) from 16 African countries. Despite high genetic diversity, the species shows stable but considerable continental population structure. Although one population showed little differentiation over a century and 4000 kilometers, nearby, we found two genetically distinct ecotypes. Vector control has resulted in strong signals of selection, with some resistance alleles shared across populations through gene flow and others arising independently. Fortunately, we found that a promising gene drive target in Anopheles gambiae is highly conserved in An. funestus. These insights will enable more strategic insecticide usage and gene drive deployment, supporting malaria elimination. 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 (see the Perspective by Carter). 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. —Corinne Simonti 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. Continental population structure among 656 modern An. funestus specimens.: PCA, fixation index (FST), and a windowed PCA approach reveal how population structure varies across the continent and along the genome. The windowed PCA shows distinct patterns for segregating inversions (including double recombinants) and loci under positive selection. Insecticide resistance mutations were found in selective sweeps on different haplotypic backgrounds, suggesting multiple independent origins, but most resistance mutations were not observed in 45 historic specimens. SNP, single-nucleotide polymorphism; L119F, Leu119Phe mutation. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.adu3596 |
