Chromosome arm specific patterns of polymorphism associated with chromosomal inversions in the major African malaria vector, Anopheles funestus

Mapping Intimacies ◽

10.1101/068205 ◽

2016 ◽

Author(s):

Colince Kamdem ◽

Caroline Fouet ◽

Bradley J. White

Keyword(s):

Chromosomal Rearrangements ◽

Anopheles Funestus ◽

Sequence Divergence ◽

Sub Saharan Africa ◽

Chromosomal Inversions ◽

Genomic Analyses ◽

Chromosome Arm ◽

Sub Saharan ◽

Moisture Conditions ◽

Two Populations

AbstractChromosomal inversions facilitate local adaptation of beneficial mutations and modulate genetic polymorphism, but the extent of their effects within the genome is still insufficiently understood. The genome of Anopheles funestus, a malaria mosquito endemic to sub-Saharan Africa, contains an impressive number of paracentric polymorphic inversions, which are unevenly distributed among chromosomes and provide an excellent framework for investigating the genomic impacts of chromosomal rearrangements. Here we present results of a fine-scale analysis of genetic variation within the genome of two weakly differentiated populations of Anopheles funestus inhabiting contrasting moisture conditions in Cameroon. Using population genomic analyses, we found that genetic divergence between the two populations is centered on regions of the genome corresponding to three inversions, which are characterized by high values of FST, absolute sequence divergence and fixed differences. Importantly, in contrast to the 2L chromosome arm, which is collinear, nucleotide diversity is significantly reduced along the entire length of three autosome arms bearing multiple overlapping chromosomal rearrangements. These findings support the idea that interactions between reduced recombination and natural selection within inversions contribute to sculpt nucleotide polymorphism across chromosomes in An. funestus.

High-Throughput Genotyping of Common Chromosomal Inversions in the Afrotropical Malaria Mosquito Anopheles Funestus

Insects ◽

10.3390/insects11100693 ◽

2020 ◽

Vol 11 (10) ◽

pp. 693

Author(s):

Martin Lukindu ◽

R. Rebecca Love ◽

Moussa W. Guelbeogo ◽

Scott T. Small ◽

Melissa T. Stephens ◽

...

Keyword(s):

High Throughput ◽

Anopheles Funestus ◽

Sub Saharan Africa ◽

Nucleotide Polymorphisms ◽

Female Population ◽

Ecotypic Differentiation ◽

Chromosomal Inversions ◽

Sub Saharan ◽

Mechanistic Basis ◽

Resting Behavior

Polymorphic chromosomal inversions have been implicated in local adaptation. In anopheline mosquitoes, inversions also contribute to epidemiologically relevant phenotypes such as resting behavior. Progress in understanding these phenotypes and their mechanistic basis has been hindered because the only available method for inversion genotyping relies on traditional cytogenetic karyotyping, a rate-limiting and technically difficult approach that is possible only for the fraction of the adult female population at the correct gonotrophic stage. Here, we focus on an understudied malaria vector of major importance in sub-Saharan Africa, Anopheles funestus. We ascertain and validate tag single nucleotide polymorphisms (SNPs) using high throughput molecular assays that allow rapid inversion genotyping of the three most common An. funestus inversions at scale, overcoming the cytogenetic karyotyping barrier. These same inversions are the only available markers for distinguishing two An. funestus ecotypes that differ in indoor resting behavior, Folonzo and Kiribina. Our new inversion genotyping tools will facilitate studies of ecotypic differentiation in An. funestus and provide a means to improve our understanding of the roles of Folonzo and Kiribina in malaria transmission.

An increasing role of pyrethroid-resistant Anopheles funestus in malaria transmission in the Lake Zone, Tanzania

Scientific Reports ◽

10.1038/s41598-021-92741-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nancy S. Matowo ◽

Jackline Martin ◽

Manisha A. Kulkarni ◽

Jacklin F. Mosha ◽

Eliud Lukole ◽

...

Keyword(s):

Malaria Transmission ◽

Anopheles Funestus ◽

Sub Saharan Africa ◽

North West ◽

Vector Population ◽

Lake Zone ◽

Sub Saharan ◽

Long Lasting Insecticidal Nets ◽

Study District

AbstractAnopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the South. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014S-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania.

Selective Introgression of Paracentric Inversions Between Two Sibling Species of the Anopheles gambiae Complex

Genetics ◽

10.1093/genetics/146.1.239 ◽

1997 ◽

Vol 146 (1) ◽

pp. 239-244

Author(s):

A della Torre ◽

L Merzagora ◽

J R Powell ◽

M Coluzzi

Keyword(s):

Anopheles Gambiae ◽

Behavioral Flexibility ◽

Introgressive Hybridization ◽

Sub Saharan Africa ◽

X Chromosomes ◽

Gambiae Complex ◽

Chromosomal Inversions ◽

Anopheles Gambiae Complex ◽

Two Generations ◽

Sub Saharan

The Anopheles gambiae complex includes the major vectors of malaria in sub-Saharan Africa where >80% of all world-wide cases occur. These mosquitoes are characterized by chromosomal inversions associated to the speciation process and to intraspecific ecological and behavioral flexibility. It has been postulated that introgressive hybridization has selectively transferred inversions on the second chromosome between A. gambiae and A. arabiensis, the two most important vectors of malaria. Here we directly test this hypothesis with laboratory experiments in which hybrid populations were established and the fate of chromosomal inversions were followed. Consistent with the hypothesis, “foreign” X chromosomes were eliminated within two generations, while some “foreign” second chromosomes persisted for the duration of the experiments and, judging from the excess of heterozygotes, established stable heterotic polymorphisms. Only those second chromosome inversions found naturally in the species could be introgressed.

Increasing role of pyrethroid-resistant Anopheles funestus in malaria transmission in the Lake Zone, Tanzania: implications for the evaluation of novel vector control products

10.1101/2021.04.01.438043 ◽

2021 ◽

Author(s):

Nancy S. Matowo ◽

Jackline Martin ◽

Manisha A. Kulkarni ◽

Jacklin F. Mosha ◽

Eliud Lukole ◽

...

Keyword(s):

Vector Control ◽

Malaria Transmission ◽

Anopheles Funestus ◽

Sub Saharan Africa ◽

North West ◽

Vector Population ◽

Lake Zone ◽

Sub Saharan ◽

Study District

AbstractAnopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the south. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014F-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania.

Mutation accumulation in chromosomal inversions maintains wing pattern polymorphism in a butterfly

10.1101/736504 ◽

2019 ◽

Cited By ~ 5

Author(s):

Paul Jay ◽

Mathieu Chouteau ◽

Annabel Whibley ◽

Héloïse Bastide ◽

Violaine Llaurens ◽

...

Keyword(s):

Chromosomal Rearrangements ◽

Mutational Load ◽

Wing Pattern ◽

Numerous Species ◽

Chromosomal Inversions ◽

Population Genomic ◽

Genomic Analyses ◽

Wing Patterns ◽

Pattern Polymorphism ◽

Genome Assemblies

While natural selection favours the fittest genotype, polymorphisms are maintained over evolutionary timescales in numerous species. Why these long-lived polymorphisms are often associated with chromosomal rearrangements remains obscure. Combining genome assemblies, population genomic analyses, and fitness assays, we studied the factors maintaining multiple mimetic morphs in the butterfly Heliconius numata. We show that the polymorphism is maintained because three chromosomal inversions controlling wing patterns express a recessive mutational load, which prevents their fixation despite their ecological advantage. Since inversions suppress recombination and hamper genetic purging, their formation fostered the capture and accumulation of deleterious variants. This suggests that many complex polymorphisms, instead of representing adaptations to the existence of alternative ecological optima, could be maintained primarily because chromosomal rearrangements are prone to carrying recessive harmful mutations.

CRISPR-mediated knock-in of transgenes into the malaria vector Anopheles funestus

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab201 ◽

2021 ◽

Author(s):

Charlotte Quinn ◽

Amalia Anthousi ◽

Charles Wondji ◽

Tony Nolan

Keyword(s):

Mosquito Species ◽

Anopheles Funestus ◽

Current Control ◽

Sub Saharan Africa ◽

Marker Genes ◽

End Joining ◽

Genetic Traits ◽

Homology Directed Repair ◽

Sub Saharan ◽

Gene Drives

Abstract The ability to introduce mutations, or transgenes, of choice to precise genomic locations has revolutionized our ability to understand how genes and organisms work. In many mosquito species that are vectors of various human diseases, the advent of CRISPR genome editing tools has shed light on basic aspects of their biology that are relevant to their efficiency as disease vectors. This allows a better understanding of how current control tools work and opens up the possibility of novel genetic control approaches, such as gene drives, that deliberately introduce genetic traits into populations. Yet for the Anopheles funestus mosquito, a significant vector of malaria in sub-Saharan Africa and indeed the dominant vector species in many countries, transgenesis has yet to be achieved. We describe herein an optimized transformation system based on the germline delivery of CRISPR components that allows efficient cleavage of a previously validated genomic site and preferential repair of these cut sites via homology-directed repair (HDR), which allows the introduction of exogenous template sequence, rather than end-joining repair. The rates of transformation achieved are sufficiently high that it should be able to introduce alleles of choice to a target locus, and recover these, without the need to include additional dominant marker genes. Moreover, the high rates of HDR observed suggest that gene drives, which employ an HDR-type mechanism to ensure their proliferation in the genome, may be well suited to work in A. funestus.

The dominant malaria vector, Anopheles funestus from rural south-eastern Tanzania, is more strongly resistant to insecticides than Anopheles arabiensis

10.21203/rs.3.rs-19762/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Polius Gerazi Pinda ◽

Claudia Eichenberger ◽

Halfan S Ngowo ◽

Dickson S Msaky ◽

Said Abbasi ◽

...

Keyword(s):

Malaria Transmission ◽

Pyrethroid Resistance ◽

Mosquito Species ◽

Anopheles Funestus ◽

Indoor Residual Spraying ◽

Sub Saharan Africa ◽

Malaria Vectors ◽

Insecticide Treated Nets ◽

South Eastern ◽

Sub Saharan

Abstract Background: Long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS) have greatly reduced malaria transmission in sub-Saharan Africa, but are threatened by insecticide resistance in dominant malaria vectors. In south-eastern Tanzania, pyrethroid-resistant Anopheles funestus now transmit more than 80% of malaria infections even in villages where the species occurs at far lower densities than other vectors such as Anopheles arabiensis.Methods: To better understand the dominance of An. funestus in these settings and improve options for its control, this study compared intensities of resistance between females of this species and those of An. arabiensis , using WHO assays with 1×, 5× and 10× insecticide doses. Additional tests were done to assess the reversibility of such resistance using synergists. The mosquitoes were collected from villages across two districts in south-eastern Tanzania.Findings: Both species were resistant to the two pyrethroids (permethrin and deltamethrin) and the organochloride (DDT) but susceptible to the organophosphate (pirimiphos-methyl) at standard baseline doses (1×). However, An. funestus as opposed to An. arabiensis was also resistant to the carbamate (bendiocarb) at standard doses (1×). An. funestus showed strong resistance to pyrethroids, surviving the 5× doses and 10× doses except in one village. Pre-exposure to the synergist, piperonyl butoxide (PBO), reversed the pyrethroid-resistance in both An. arabiensis and An. funestus achieving mortalities >98%, except for An. funestus from two villages for which permethrin-associated mortalities exceeded 90% but not 98%.Conclusions : In these communities where An. funestus now dominates malaria transmission, the species also displays much stronger resistance to pyrethroids than its counterpart, An. arabiensis, and can readily survive more classes of insecticides, including carbamates. The resistance to pyrethroids in both mosquito species appears to be mostly metabolic and can be reversed significantly using synergists such as PBO. These findings may explain the continued persistence and dominance of An. funestus despite widespread use of pyrethroid-treated LLINs, and will also inform future choices of interventions to tackle malaria transmission in this area and other similar settings. Such interventions may include PBO-based LLINs or improved IRS with compounds such as organophosphates against which the vectors are still susceptible.

Chromosome arm-specific patterns of polymorphism associated with chromosomal inversions in the major African malaria vector,Anopheles funestus

Molecular Ecology ◽

10.1111/mec.14335 ◽

2017 ◽

Vol 26 (20) ◽

pp. 5552-5566 ◽

Cited By ~ 5

Author(s):

Colince Kamdem ◽

Caroline Fouet ◽

Bradley J. White

Keyword(s):

Malaria Vector ◽

Anopheles Funestus ◽

Chromosomal Inversions ◽

Chromosome Arm

CRISPR-mediated knock-in of transgenes into the malaria vector Anopheles funestus

10.1101/2021.03.31.437891 ◽

2021 ◽

Author(s):

Charlotte Quinn ◽

Amalia Anthousi ◽

Charles Wondji ◽

Tony Nolan

Keyword(s):

Mosquito Species ◽

Anopheles Funestus ◽

Current Control ◽

Sub Saharan Africa ◽

Marker Genes ◽

End Joining ◽

Genetic Traits ◽

Homology Directed Repair ◽

Sub Saharan ◽

Gene Drives

ABSTRACTThe ability to introduce mutations, or transgenes, of choice to precise genomic locations has revolutionised our ability to understand how genes and organisms work.In many mosquito species that are vectors of various human disease, the advent of CRISPR genome editing tools has shed light on basic aspects of their biology that are relevant to their efficiency as disease vectors. This allows a better understanding of how current control tools work and opens up the possibility of novel genetic control approaches, such as gene drives, that deliberately introduce genetic traits into populations. Yet for the Anopheles funestus mosquito, a significant vector of malaria in sub-Saharan Africa and indeed the dominant vector species in many countries, transgenesis has yet to be achieved.We describe herein an optimised transformation system based on the germline delivery of CRISPR components that allows efficient cleavage of a previously validated genomic site and preferential repair of these cut sites via homology-directed repair (HDR), which allows introduction of exogenous template sequence, rather than end-joining repair. The rates of transformation achieved are sufficiently high that it should be able to introduce alleles of choice to a target locus, and recover these, without the need to include additional dominant marker genes. Moreover, the high rates of HDR observed suggest that gene drives, which employ an HDR-type mechanism to ensure their proliferation in the genome, may be well suited to work in An. funestus.

Seasonal hunger among the Ngoni and Ntumba of central Malaŵi

Africa ◽

10.2307/1158776 ◽

1975 ◽

Vol 45 (1) ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

G. T. Nurse

Keyword(s):

Critical Level ◽

Sub Saharan Africa ◽

Agricultural Workers ◽

Cultural Significance ◽

Tropical Africa ◽

Long Time ◽

Sub Saharan ◽

Opening Paragraph ◽

Two Populations ◽

High Storage

Opening ParagraphThe cultural significance of regular ‘hunger periods’ in tropical Africa, however much it may be disputed by anthropologists, has for a long time been apparent to less objective observers. It is generally accepted by those concerned in the engagement of migrant labour that at certain regular times of the year the supply is greater than at others: and it is believed that the number of men presenting for engagement is related to the quantity of food available in the villages. This view, as will be shown below, is an over-simplification. Ogbu (1973), though he relates seasonal hunger among the Poka to labour migration, sees die latter as a cause rather than a result of the former. He apparently considers that migration reduces the number of agricultural workers to below an unstipulated critical level above which it might still be possible to produce a sufficiency of food at all seasons, provided that animal pests could be controlled and agricultural techniques made more efficient. Seasonal hunger among the Ibo of Onicha he blames on shortage of farmland, low yield, and high storage loss of foodstuffs. At first sight it might appear that the cultural concomitants of the hunger period contrast rather strikingly between the two populations; and yet the recurrent hunger period is recognized by the FAO and other authorities (though Miracle (1961) questions its existence) as being a phenomenon widespread in sub- Saharan Africa, and one which might in consequence be expected to result from similar or related causes in most of the situations in which it occurs.