Reticulate speciation and adaptive introgression in the Anopheles gambiae species complex

Anopheles gambiae, the primary vector of human malaria in sub-Saharan Africa, exists as a series of ecologically specialized subgroups that are phylogenetically nested within the Anopheles gambiae species complex. These species and subgroups exhibit varying degrees of reproductive isolation, sometimes recognized as distinct subspecies. We have sequenced 32 complete genomes from field-captured individuals of Anopheles gambiae, Anopheles gambiae M form (recently named A. coluzzii), sister species A. arabiensis, and the recently discovered ?GOUNDRY? subgroup of A. gambiae that is highly susceptible to Plasmodium. Amidst a backdrop of strong reproductive isolation and adaptive differentiation, we find evidence for introgression of autosomal chromosomal regions among species and subgroups, some of which have facilitated adaptation. The X chromosome, however, is strongly differentiated among all species and subgroups, pointing to a disproportionately large effect of X chromosome genes in driving speciation among anophelines. Strikingly, we find that autosomal introgression has occurred from contemporary hybridization among A. gambiae and A. arabiensis despite strong divergence (~5? higher than autosomal divergence) and isolation on the X chromosome. We find a large region of the X chromosome that has swept to fixation in the GOUNDRY subgroup within the last 100 years, which may be an inversion that serves as a partial barrier to contemporary gene flow. We show that speciation with gene flow results in genomic mosaicism of divergence and introgression. Such a reticulate gene pool connecting vector species and subgroups across the speciation continuum has important implications for malaria control efforts.

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Anopheles gambiae (Ag55) cells are phagocytic and have hemocyte-like gene expression

10.21203/rs.2.24674/v1 ◽

2020 ◽

Author(s):

Michael J. Adang ◽

Ruchir Mishra ◽

Gang Hua ◽

Urjwal R. Bagal ◽

Don Champagne

Keyword(s):

Gene Expression ◽

Anopheles Gambiae ◽

Cell Lines ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Sub Saharan Africa ◽

Transcriptomic Data ◽

Kegg Pathway Analysis ◽

Primary Vector ◽

Sub Saharan

Abstract Background Anopheles gambiae is the predominant vector of malaria, the fourth largest cause of infant mortality, in sub- Saharan Africa. Furthermore, A. gambiae is also the primary vector of O'nyong-nyong virus. The complexity of handling A. gambiae and infectious pathogens has led to the use of A. gambiae cell lines, including Ag55 cells, as a potential model to study vector-pathogen interactions and immune responses. The utility of cell lines can be maximized if their detailed gene expression profile and properties are available. Results We provide detailed gene expression profiles, proteome and information about the properties of Ag55 cells. KEGG pathway analysis on genes with transcript levels of ≥200 FPKM revealed phagosome term enriched. Further, transcriptomic data backed by confocal microscopy and flow cytometry suggest that Ag55 cells have are hemocyte-like with phagocytic properties and immune competence. Conclusion As Ag55 cells are immune competent and express hemocyte like properties they can be used as a model to study vector-pathogen immune response. Furthermore, the availability of transcriptomic data of Ag55 cells will help researchers use and engineer the Ag55 cell line in an efficient way, for example by developing strategies to make it more suitable for studies of interactions with Plasmodium and other microbes.

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Ecological drivers of genetic connectivity for African malaria vectors Anopheles gambiae and An. arabiensis

Scientific Reports ◽

10.1038/s41598-020-76248-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Elizabeth Hemming-Schroeder ◽

Daibin Zhong ◽

Maxwell Machani ◽

Hoan Nguyen ◽

Sarah Thong ◽

...

Keyword(s):

Genetic Diversity ◽

Gene Flow ◽

Anopheles Gambiae ◽

Population Genetic ◽

Sub Saharan Africa ◽

Tree Cover ◽

Genetic Connectivity ◽

Malaria Vectors ◽

Western Kenya ◽

Sub Saharan

AbstractAnopheles gambiae and An. arabiensis are major malaria vectors in sub-Saharan Africa. Knowledge of how geographical factors drive the dispersal and gene flow of malaria vectors can help in combatting insecticide resistance spread and planning new vector control interventions. Here, we used a landscape genetics approach to investigate population relatedness and genetic connectivity of An. gambiae and An. arabiensis across Kenya and determined the changes in mosquito population genetic diversity after 20 years of intensive malaria control efforts. We found a significant reduction in genetic diversity in An. gambiae, but not in An. arabiensis as compared to prior to the 20-year period in western Kenya. Significant population structure among populations was found for both species. The most important ecological driver for dispersal and gene flow of An. gambiae and An. arabiensis was tree cover and cropland, respectively. These findings highlight that human induced environmental modifications may enhance genetic connectivity of malaria vectors.

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Characterizing Permethrin and Etofenprox Resistance in Two Common Laboratory Strains of Anopheles gambiae (Diptera: Culicidae)

Insects ◽

10.3390/insects9040146 ◽

2018 ◽

Vol 9 (4) ◽

pp. 146 ◽

Cited By ~ 3

Author(s):

Aaron Gross ◽

Jeffrey Bloomquist

Keyword(s):

Anopheles Gambiae ◽

Pyrethroid Resistance ◽

Laboratory Strain ◽

Pyrethroid Insecticide ◽

Sub Saharan Africa ◽

Cross Resistance ◽

Type I ◽

Mosquito Vector ◽

Sub Saharan ◽

Anopheles Gambiae Giles

Anopheles gambiae Giles (Diptera: Culicidae) is the most prolific malaria vector in sub-Saharan Africa, where widespread insecticide resistance has been reported. An. gambiae laboratory strains are commonly used to study the basic biology of this important mosquito vector, and also in new insecticide discovery programs, where insecticide-susceptible and -resistant strains are often used to screen new molecules for potency and cross-resistance, respectively. This study investigated the toxicity of permethrin, a Type-I pyrethroid insecticide, and etofenprox, a non-ester containing pyrethroid insecticide, against An. gambiae at three life stages. This characterization was performed with susceptible (G3; MRA-112) and resistant (Akdr; MRA-1280) An. gambiae strains; the Akdr strain is known to contain the L1014F mutation in the voltage-sensitive sodium channel. Surprisingly, etofenprox displays a lower level of resistance than permethrin against all stages of mosquitoes, except in a headless larval paralysis assay designed to minimize penetration factors. In first-instar An. gambiae larvae, permethrin had significant resistance, determined by the resistance ratio (RR50 = 5), but etofenprox was not significantly different (RR50 = 3.4) from the wild-type strain. Fourth-instar larvae displayed the highest level of resistance for permethrin (RR50 = 108) and etofenprox (RR50 = 35). Permethrin (PC50 = 2 ppb) and etofenprox (PC50 = 9 ppb) resulted in headless larval paralysis (5-h), but resistance, albeit lower, was still present for permethrin (RR50 = 5) and etofenprox (RR50 = 6.9). In adult female mosquitoes, permethrin displayed higher resistance (RR50 = 14) compared to etofenprox (RR50 = 4.3). The level of etofenprox resistance was different from that previously reported for a similar Akron An. gambiae laboratory strain (MRA-913). The chemical synergists piperonyl butoxide (PBO) and diethyl maleate (DEM) were able to synergize permethrin, but not etofenprox in the resistant strain (Akdr). In conclusion, multiple mechanisms are likely involved in pyrethroid resistance, but resistance profiles are dependent upon selection. Etofenprox is an effective insecticide against An. gambiae in the lab but will likely suffer from resistance in the field.

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Admixture into and within sub-Saharan Africa

eLife ◽

10.7554/elife.15266 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 57

Author(s):

George BJ Busby ◽

Gavin Band ◽

Quang Si Le ◽

Muminatou Jallow ◽

Edith Bougama ◽

...

Keyword(s):

Gene Flow ◽

Geographic Region ◽

Sub Saharan Africa ◽

Genome Wide ◽

A Genome ◽

Depth Analysis ◽

Shared Ancestry ◽

Sub Saharan ◽

Linguistic Groups ◽

Insight Into

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology.

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CLIPB10 is a Terminal Protease in the Regulatory Network That Controls Melanization in the African Malaria Mosquito Anopheles gambiae

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.585986 ◽

2021 ◽

Vol 10 ◽

Author(s):

Xin Zhang ◽

Miao Li ◽

Layla El Moussawi ◽

Sally Saab ◽

Shasha Zhang ◽

...

Keyword(s):

Anopheles Gambiae ◽

Serine Proteases ◽

Ex Vivo ◽

Protein A ◽

Tumor Formation ◽

Sub Saharan Africa ◽

Humoral Immune ◽

Wide Range ◽

Sub Saharan

Humoral immune responses in animals are often tightly controlled by regulated proteolysis. This proteolysis is exerted by extracellular protease cascades, whose activation culminates in the proteolytic cleavage of key immune proteins and enzymes. A model for such immune system regulation is the melanization reaction in insects, where the activation of prophenoxidase (proPO) leads to the rapid formation of eumelanin on the surface of foreign entities such as parasites, bacteria and fungi. ProPO activation is tightly regulated by a network of so-called clip domain serine proteases, their proteolytically inactive homologs, and their serpin inhibitors. In Anopheles gambiae, the major malaria vector in sub-Saharan Africa, manipulation of this protease network affects resistance to a wide range of microorganisms, as well as host survival. However, thus far, our understanding of the molecular make-up and regulation of the protease network in mosquitoes is limited. Here, we report the function of the clip domain serine protease CLIPB10 in this network, using a combination of genetic and biochemical assays. CLIPB10 knockdown partially reversed melanotic tumor formation induced by Serpin 2 silencing in the absence of infection. CLIPB10 was also partially required for the melanization of ookinete stages of the rodent malaria parasite Plasmodium berghei in a refractory mosquito genetic background. Recombinant serpin 2 protein, a key inhibitor of the proPO activation cascade in An. gambiae, formed a SDS-stable protein complex with activated recombinant CLIPB10, and efficiently inhibited CLIPB10 activity in vitro at a stoichiometry of 1.89:1. Recombinant activated CLIPB10 increased PO activity in Manduca sexta hemolymph ex vivo, and directly activated purified M. sexta proPO in vitro. Taken together, these data identify CLIPB10 as the second protease with prophenoloxidase-activating function in An. gambiae, in addition to the previously described CLIPB9, suggesting functional redundancy in the protease network that controls melanization. In addition, our data suggest that tissue melanization and humoral melanization of parasites are at least partially mediated by the same proteases.

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Pyrethroid Resistance in Anopheles gambiae Not Associated with Insecticide-Treated Mosquito Net Effectiveness Across Sub-Saharan Africa

SSRN Electronic Journal ◽

10.2139/ssrn.3559606 ◽

2020 ◽

Author(s):

David A. Larsen ◽

Rachel L. Church

Keyword(s):

Anopheles Gambiae ◽

Pyrethroid Resistance ◽

Sub Saharan Africa ◽

Mosquito Net ◽

Sub Saharan

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Ancestral and neo-sex chromosomes contribute to population divergence in a dioecious plant

10.1101/550962 ◽

2019 ◽

Cited By ~ 2

Author(s):

Felix E.G. Beaudry ◽

Spencer C.H. Barrett ◽

Stephen I. Wright

Keyword(s):

Gene Flow ◽

Reproductive Isolation ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Demographic History ◽

Population Divergence ◽

Effective Population ◽

Dioecious Plant ◽

Fusion Event ◽

Contemporary Gene Flow

ABSTRACTEmpirical evidence from several animal groups suggests that sex chromosomes may disproportionately contribute to reproductive isolation. This occurs particularly when sex chromosomes are associated with turnover of sex determination systems resulting from structural rearrangements to the sex chromosomes. We investigated these predictions in the dioecious plant Rumex hastatulus, which is comprised of populations of two sex chromosome cytotypes. Using population genomic analyses, we investigated the demographic history of R. hastatulus and explored the contributions of ancestral and neo-sex chromosomes to population genetic divergence. Our study revealed that the cytotypes represented genetically divergent populations with evidence for historical but not contemporary gene flow between them. In agreement with classical predictions, we found that the ancestral X chromosome was disproportionately divergent compared with the rest of the genome. Excess differentiation was also observed on the Y chromosome, even when using measures of differentiation that control for differences in effective population size. Our estimates of the timing of the origin of the neo-sex chromosomes in R. hastatulus are coincident with cessation of gene flow, suggesting that the chromosomal fusion event that gave rise to the origin of the XYY cytotype may have also been a key driver of reproductive isolation.

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The genetic architecture of post-zygotic reproductive isolation between Anopheles coluzzii and An. quadriannulatus

10.1101/2020.05.19.104786 ◽

2020 ◽

Author(s):

Kevin C. Deitz ◽

Willem Takken ◽

Michel A. Slotman

Keyword(s):

Reproductive Isolation ◽

Anopheles Gambiae ◽

X Chromosome ◽

Genetic Background ◽

Epistatic Interaction ◽

Hybrid Sterility ◽

Anopheles Coluzzii ◽

Hybrid Male ◽

Backcross Population ◽

Complex Species

AbstractThe Anopheles gambiae complex is comprised of eight morphologically indistinguishable species and has emerged as a model system for the study of speciation genetics due to the rapid radiation of its member species over the past two million years. Male hybrids between most An. gambiae complex species pairs are sterile, and some genotype combinations in hybrid males cause inviability. We investigated the genetic basis of hybrid male inviability and sterility between An. coluzzii and An. quadriannulatus by measuring segregation distortion and performing a QTL analysis of sterility in a backcross population. Hybrid males were inviable if they inherited the An. coluzzii X chromosome and were homozygous at one or more loci in 18.9 Mb region of chromosome 3. The An. coluzzii X chromosome has a disproportionately large effect on hybrid sterility when introgressed into an An. quadriannulatus genetic background. Additionally, an epistatic interaction between the An. coluzzii X and a 1.12 Mb, pericentric region of the An. quadriannulatus 3L chromosome arm has a statistically significant contribution to the hybrid sterility phenotype. This same epistatic interaction occurs when the An. coluzzii X is introgressed into the genetic background of An. arabiensis, the sister species of An. quadriannulatus, suggesting that this may represent one of the first Dobzhansky–Muller incompatibilities to evolve early in the radiation of the Anopheles gambiae species complex. We describe the additive effects of each sterility QTL, epistatic interactions between them, and genes within QTL with protein functions related to mating behavior, reproduction, spermatogenesis, and microtubule morphogenesis, whose divergence may contribute to post-zygotic reproductive isolation between An. coluzzii and An. quadriannulatus.

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Justifying an Intentional Species Extinction: The Case of Anopheles gambiae

Environmental Values ◽

10.3197/096327121x16081160834786 ◽

2021 ◽

Author(s):

Daniel Edward Callies ◽

Yasha Rohwer

Keyword(s):

Anopheles Gambiae ◽

Malaria Vector ◽

Malaria Parasite ◽

Sub Saharan Africa ◽

Species Extinction ◽

Malaria Burden ◽

Subjective Value ◽

The World ◽

Genetic Technologies ◽

Sub Saharan

Each year, over 200 million people are infected with the malaria parasite, nearly half a million of whom succumb to the disease. Emerging genetic technologies could, in theory, eliminate the burden of malaria throughout the world by intentionally eradicating the mosquitoes that transmit the disease. In this paper, we offer an ethical examination of the intentional eradication of Anopheles gambiae, the main malaria vector of sub-Saharan Africa. In our evaluation, we focus on two main considerations: the benefit of alleviating the malaria burden, and the loss of value that would accompany the eradication of the species. We outline a typology of the different ways in which species are valued or could be valuable, then use that typology to appraise the value of the species in question. We argue that Anopheles gambiae has minor (and redundant) instrumental value, little final subjective value and no objective final value.

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