A
            <i>Plasmodium</i>
            key fits a mosquito lock

Jae, Sung Myung; Jacobs-­Lorena, Marcelo

doi:10.1073/pnas.2000122117

Cited by 2 publications

(2 citation statements)

References 7 publications

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“…A cysteine-rich AMP named gambicin was marginally lethal to Plasmodium berghei ookinetes [ 11 ]. Despite these defense mechanisms, P. falciparum is still well able to evade detection by mosquito immunity complexes through the action of the Pfs47 surface protein and mosquito receptor in a ‘lock and key’ fashion [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Gene Conversion Explains Elevated Diversity in the Immunity Modulating APL1 Gene of the Malaria Vector Anopheles funestus

Hearn

Riveron

Irving

et al. 2022

Genes

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Leucine-rich repeat proteins and antimicrobial peptides are the key components of the innate immune response to Plasmodium and other microbial pathogens in Anopheles mosquitoes. The APL1 gene of the malaria vector Anopheles funestus has exceptional levels of non-synonymous polymorphism across the range of An. funestus, with an average πn of 0.027 versus a genome-wide average of 0.002, and πn is consistently high in populations across Africa. Elevated APL1 diversity was consistent between the independent pooled-template and target-enrichment datasets, however no link between APL1 diversity and insecticide resistance was observed. Although lacking the diversity of APL1, two further mosquito innate-immunity genes of the gambicin anti-microbial peptide family had πn/πs ratios greater than one, possibly driven by either positive or balancing selection. The cecropin antimicrobial peptides were expressed much more highly than other anti-microbial peptide genes, a result discordant with current models of anti-microbial peptide activity. The observed APL1 diversity likely results from gene conversion between paralogues, as evidenced by shared polymorphisms, overlapping read mappings, and recombination events among paralogues. In conclusion, we hypothesize that higher gene expression of APL1 than its paralogues is correlated with a more open chromatin formation, which enhances gene conversion and elevated diversity at this locus.

show abstract

Section: Introductionmentioning

confidence: 99%

Gene Conversion Explains Elevated Diversity in the Immunity Modulating APL1 Gene of the Malaria Vector Anopheles funestus

Hearn

Riveron

Irving

et al. 2022

Genes

View full text Add to dashboard Cite

show abstract

“…A cysteine-rich AMP named gambicin was marginally lethal to P. berghei ookinetes (Vizioli et al 2001). Despite these defence mechanisms, P. falciparum is still well able to evade detection by mosquito immunity complexes through the action of Pfs47 surface protein and mosquito receptor in a ‘lock and key’ fashion (Molina-Cruz et al 2013; Cha & Jacobs-Lorena 2020).…”

Section: Introductionmentioning

confidence: 99%

Gene conversion explains elevated diversity in the immunity modulating APL1 gene of the malaria vector Anopheles funestus

Hearn

Riveron

Irving

et al. 2021

Preprint

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The leucine rich repeat gene APL1 is a key component of immunity to Plasmodium and other microbial pathogens in Anopheles mosquitoes. In the malaria vector Anopheles funestus the APL1 gene has four paralogues which occur along the same chromosome arm. We show that APL1 has exceptional levels of non-synonymous polymorphism across the range of An. funestus with an average πn of 0.027 versus a genome-wide average of 0.002, and πn (and πs) is consistently high in populations across Africa. The pattern of APL1 diversity was consistent between independent pooled-template and target-enrichment datasets, however no link between APL1 diversity and insecticide-resistance was observed with the phenotyped target-enrichment dataset. Two further innate immunity genes of the gambicin anti-microbial peptide family had πn/πs ratios greater than one, possibly driven by either positive or balancing selection. Cecropin antimicrobial peptides were expressed much more highly than other anti-microbial peptide genes, an observation discordant with current models of anti-microbial peptide activity. The observed APL1 diversity likely results from gene conversion between paralogs, as evidenced by shared polymorphisms, overlapping read mappings, and recombination events among paralogues. Gene conversion at APL1 versus alternative explanations is concordant with similarly elevated diversity in APL1 and TEP1 loci in An. gambiae. In contrast, the more closely related An. stephensi which also encodes a single-copy of APL1 does not show this elevated diversity. We hypothesise that a more open chromatin formation at the APL1 locus due to higher gene expression than its paralogues enhances gene conversion, and therefore increased polymorphism, at APL1.

show abstract

A Plasmodium key fits a mosquito lock

Cited by 2 publications

References 7 publications

Gene Conversion Explains Elevated Diversity in the Immunity Modulating APL1 Gene of the Malaria Vector Anopheles funestus

Gene Conversion Explains Elevated Diversity in the Immunity Modulating APL1 Gene of the Malaria Vector Anopheles funestus

Gene conversion explains elevated diversity in the immunity modulating APL1 gene of the malaria vector Anopheles funestus

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