Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

Handle URI:
http://hdl.handle.net/10754/348500
Title:
Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response
Authors:
Juneja, Punita; Ariani, Cristina V.; Ho, Yung Shwen; Akorli, Jewelna; Palmer, William J.; Pain, Arnab ( 0000-0002-1755-2819 ) ; Jiggins, Francis M.
Abstract:
Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response 2015, 11 (3):e1004765 PLOS Pathogens
Publisher:
Public Library of Science (PLoS)
Journal:
PLOS Pathogens
Issue Date:
27-Mar-2015
DOI:
10.1371/journal.ppat.1004765
PubMed ID:
25815506
PubMed Central ID:
PMC4376896
Type:
Article
ISSN:
1553-7374
Additional Links:
http://dx.plos.org/10.1371/journal.ppat.1004765
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorJuneja, Punitaen
dc.contributor.authorAriani, Cristina V.en
dc.contributor.authorHo, Yung Shwenen
dc.contributor.authorAkorli, Jewelnaen
dc.contributor.authorPalmer, William J.en
dc.contributor.authorPain, Arnaben
dc.contributor.authorJiggins, Francis M.en
dc.date.accessioned2015-04-05T07:52:43Zen
dc.date.available2015-04-05T07:52:43Zen
dc.date.issued2015-03-27en
dc.identifier.citationExome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response 2015, 11 (3):e1004765 PLOS Pathogensen
dc.identifier.issn1553-7374en
dc.identifier.pmid25815506en
dc.identifier.doi10.1371/journal.ppat.1004765en
dc.identifier.urihttp://hdl.handle.net/10754/348500en
dc.description.abstractMany mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.en
dc.publisherPublic Library of Science (PLoS)en
dc.relation.urlhttp://dx.plos.org/10.1371/journal.ppat.1004765en
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. http://creativecommons.org/licenses/by/4.0/en
dc.titleExome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Responseen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalPLOS Pathogensen
dc.identifier.pmcidPMC4376896en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Genetics, University of Cambridge, Cambridge, United Kingdomen
dc.contributor.institutionDepartment of Parasitology, Noguchi Memorial Institute for Medical Research, Accra, Ghanaen
kaust.authorPain, Arnaben
kaust.authorHo, Yungshwenen

Related articles on PubMed

All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.