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SNP discovery and molecular evolution in Anopheles gambiae, with special emphasis on innate immune system.

ABSTRACT: BACKGROUND: Anopheles innate immunity affects Plasmodium development and is a potential target of innovative malaria control strategies. The extent and distribution of nucleotide diversity in immunity genes might provide insights into the evolutionary forces that condition pathogen-vector interactions. The discovery of polymorphisms is an essential step towards association studies of susceptibility to infection. RESULTS: We sequenced coding fragments of 72 immune related genes in natural populations of Anopheles gambiae and of 37 randomly chosen genes to provide a background measure of genetic diversity across the genome. Mean nucleotide diversity (pi) was 0.0092 in the A. gambiae S form, 0.0076 in the M form and 0.0064 in A. arabiensis. Within each species, no statistically significant differences in mean nucleotide diversity were detected between immune related and non immune related genes. Strong purifying selection was detected in genes of both categories, presumably reflecting strong functional constraints. CONCLUSION: Our results suggest similar patterns and rates of molecular evolution in immune and non-immune genes in A. gambiae. The 3,214 Single Nucleotide Polymorphisms (SNPs) that we identified are the first large set of Anopheles SNPs from fresh, field-collected material and are relevant markers for future phenotype-association studies.

SUBMITTER: Cohuet A

PROVIDER: S-EPMC2405807 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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SNP discovery and molecular evolution in Anopheles gambiae, with special emphasis on innate immune system.

Cohuet Anna A Krishnakumar Sujatha S Simard Frédéric F Morlais Isabelle I Koutsos Anastasios A Fontenille Didier D Mindrinos Michael M Kafatos Fotis C FC

BMC genomics 20080519

<h4>Background</h4>Anopheles innate immunity affects Plasmodium development and is a potential target of innovative malaria control strategies. The extent and distribution of nucleotide diversity in immunity genes might provide insights into the evolutionary forces that condition pathogen-vector interactions. The discovery of polymorphisms is an essential step towards association studies of susceptibility to infection.<h4>Results</h4>We sequenced coding fragments of 72 immune related genes in na ...[more]

PMID: 18489733

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Project description:As pathogens that circumvent the host immune response are favoured by selection, so are host alleles that reduce parasite load. Such evolutionary processes leave their signature on the genes involved. Deciphering modes of selection operating on immune genes might reveal the nature of host-pathogen interactions and factors that govern susceptibility in host populations. Such understanding would have important public health implications.We analyzed polymorphisms in four mosquito immune genes (SP14D1, GNBP, defensin, and gambicin) to decipher selection effects, presumably mediated by pathogens. Using samples of Anopheles arabiensis, An. quadriannulatus and four An. gambiae populations, as well as published sequences from other Culicidae, we contrasted patterns of polymorphisms between different functional units of the same gene within and between populations. Our results revealed selection signatures operating on different time scales. At the most recent time scale, within-population diversity revealed purifying selection. Between populations and between species variation revealed reduced differentiation (GNBP and gambicin) at coding vs. noncoding- regions, consistent with balancing selection. McDonald-Kreitman tests between An. quadriannulatus and both sibling species revealed higher fixation rate of synonymous than nonsynonymous substitutions (GNBP) in accordance with frequency dependent balancing selection. At the longest time scale (>100 my), PAML analysis using distant Culicid taxa revealed positive selection at one codon in gambicin. Patterns of genetic variation were independent of exposure to human pathogens.Purifying selection is the most common form of selection operating on immune genes as it was detected on a contemporary time scale on all genes. Selection for "hypervariability" was not detected, but negative balancing selection, detected at a recent evolutionary time scale between sibling species may be rather common. Detection of positive selection at the deepest evolutionary time scale suggests that it occurs infrequently, possibly in association with speciation events. Our results provided no evidence to support the hypothesis that selection was mediated by pathogens that are transmitted to humans.

Project description:Blood feeding is an integral behavior of mosquitoes to acquire nutritional resources needed for reproduction. This requirement also enables mosquitoes to serve as efficient vectors to acquire and potentially transmit a multitude of mosquito-borne diseases, most notably malaria. Recent studies suggest that mosquito immunity is stimulated following a blood meal, independent of infection status. Since blood feeding promotes production of the hormone 20-hydroxyecdysone (20E), we hypothesized that 20E plays an important role in priming the immune response for pathogen challenge. Here, we examine the immunological effects of priming Anopheles gambiae with 20E prior to pathogen infection, demonstrating a significant reduction in bacteria and Plasmodium berghei survival in the mosquito host. Transcriptome sequencing (RNA-seq) analysis following 20E treatment identifies several known 20E-regulated genes, as well as several immune genes with previously reported function in antipathogen defense. Together, these data demonstrate that 20E influences cellular immune function and antipathogen immunity following mosquito blood feeding, arguing the importance of hormones in the regulation of mosquito innate immune function.IMPORTANCE Blood feeding is required to provide nutrients for mosquito egg production and serves as a mechanism to acquire and transmit pathogens. Shortly after a blood meal is taken, there is a peak in the production of 20-hydroxyecdysone (20E), a mosquito hormone that initiates physiological changes, including yolk protein production and mating refractoriness. Here, we examine additional roles of 20E in the regulation of mosquito immunity, demonstrating that priming the immune system with 20E increases mosquito resistance to pathogens. We identify differentially expressed genes in response to 20E treatment, including several involved in innate immune function as well as lipid metabolism and transport. Together, these data argue that 20E stimulates mosquito cellular immune function and innate immunity shortly after blood feeding.

Dataset Information

SNP discovery and molecular evolution in Anopheles gambiae, with special emphasis on innate immune system.

Publications

SNP discovery and molecular evolution in Anopheles gambiae, with special emphasis on innate immune system.

Similar Datasets

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