Genomics and Pathogenomics of the Culex Mosquito

Genomics and Pathogenomics of the Culex Mosquito: a blood-sucking transmitter of elephantiasis-causing worms and encephalitis-inducing viruses

Mosquitoes are the most important disease-vectors, with Culex, Aedes, and Anopheles species transmitting many different human pathogens including those that cause malaria, dengue and yellow fever, West Nile encephalitis, and lymphatic filariasis. Sequencing the genome of the Culex quinquefasciatus mosquito achieves the important goal of obtaining a complete reference genome from each of these three major taxonomic groups of disease-vector mosquitoes. Two studies published on October 1st in the journal Science exploited these sequencing data to compare the genomes and encoded genes, and the responses to pathogen infections, of the Culex quinquefasciatus mosquito with those of the malaria mosquito, Anopheles gambiae, and the dengue mosquito, Aedes aegypti.

The two studies involved a total of almost 90 international scientists, with the genome project researchers collaborating under the leadership of Peter Atkinson and Peter Arensburger from the University of California Riverside, and the pathogenomics project team led by Marc Muskavitch from Boston College, the Broad Institute, and Harvard School of Public Health, Lyric Bartholomay from Iowa State University, and Robert Waterhouse from the University of Geneva Medical School and the Swiss Institute of Bioinformatics.

Culex quinquefasciatus mosquitoes present a significant threat to both human and veterinary health”, says Atkinson, “as they are primary vectors of West Nile virus, the filarial worm Wuchereria bancrofti, and the avian malaria parasite, Plasmodium relictum”. Although most humans infected with West Nile virus are symptom-free, some may suffer a fever, but in rare cases where the infection becomes neuroinvasive it can develop into life-threatening West Nile encephalitis. Filarial worms transmitted to humans through the bite of an infected mosquito cause damage to lymphatic vessels resulting in swelling that in severe cases leads to debilitating elephantiasis. Since the introduction of Culex quinquefasciatus to the Hawaiian islands in 1826, avian malaria caused by Plasmodium relictum has resulted in the extinction of many native bird species. According to Muskavitch, “As a geographically widespread species that is capable of transmitting diverse pathogens including filarial worms, malaria parasites and several different viruses, Culex quinquefasciatus is a significant global public health concern”.

“The Culex quinquefasciatus genome project revealed a repertoire of 18,883 protein-coding genes”, says Arensburger, “this is 22% larger than that of Aedes aegypti and 52% larger than that of Anopheles gambiae”. The genome project researchers discovered that the increased gene numbers in Culex quinquefasciatus are partly explained by the presence of expanded gene families of olfactory (smell) and gustatory (taste) receptors, several types of immune-related genes, as well as genes with possible roles in drug metabolism that could influence resistance to insecticides. “The wide range of smell and taste receptors”, adds Arensburger, “may explain the opportunistic blood-feeding behaviour of Culex quinquefasciatus females, which are able to detect and feed upon birds, humans and livestock”.

“Our pathogenomics study took advantage of the sequencing of the Culex quinquefasciatus genome” says Muskavitch, “to bring together data from experiments profiling responses of mosquito genes to pathogen infections directed by Professor Bartholomay with the results of comparative immunogenomics analyses led by Dr Waterhouse”. This unprecedented study of 25 vector-pathogen interactions involving viruses, filarial worms, bacteria and malaria parasites, revealed common and distinct responses to these pathogen types in the three mosquito species. “We applied our experience from the comparative evolutionary genomic analyses of insects”, says Professor Zdobnov from the University of Geneva Medical School and the Swiss Institute of Bioinformatics, “to characterise the expanded immune gene repertoire of Culex quinquefasciatus”. Waterhouse explains that “The apparent diversification of immune surveillance and signal amplification genes may enhance the ability of Culex quinquefasciatus to adapt to diverse habitats with different pathogen challenges”. Bartholomay concludes that “Examining both native and non-native vector-pathogen interactions, our results strongly support the hypothesis that pathogens that successfully develop in, and are transmitted by, disease-vector mosquitoes, have evolved to avoid most mosquito immune responses”.

These two studies reveal how the sequencing of the Culex quinquefasciatus genome will greatly facilitate detailed experimental investigations to uncover the complex biology of this important disease-vector mosquito. It establishes a platform for mosquito comparative genomics across the three major taxonomic groups of mosquitoes, which are responsible for the vast majority of human morbidity and mortality attributable to insect-transmitted pathogens.

Links: People

University of Geneva & Swiss Institute of Bioinformatics: Robert Waterhouse & Evgeny Zdobnov - EurekAlert!
University of California Riverside: Peter Atkinson & Peter Arensburger - EurekAlert!
Boston College: Marc Muskavitch - EurekAlert!
Iowa State University: Lyric Bartholomay - ISU Media

Links: Press

Swiss Institute of Bioinformatics: NewsRoom English French German
Actualités Unige (en français) L’un des principaux vecteurs de maladies, le moustique Culex, révèle les secrets de son système immunitaire
Science Editorial Closing the Vector Circle
Broad Institute Completing a disease mosquito genome trifecta
GEN News Genetic Engineering & Biotechnology News
GenomeWeb International Team Sequences Genome of West Nile-Transmitting Mosquito
Science Daily Genome of Mosquito That Spreads West Nile Virus Sequenced
Science News New genetic blueprint for bloodsuckers
Tribune de Genève (en français) Trois moustiques tueurs rattrapés par leur génome
Television Suisse Romande (en français) Séquençage du génome du moustique vecteur du virus du Nil occidental
Ordine dei Medici (in italiano) Virus del Nilo Occidentale ed Encefalite: Sequenziato il genoma della zanzara che li causa
El Mundo (en Español) Los tres mosqueteros de las enfermedades tropicales
Último Segundo (em português) Cientistas sequenciam o genoma do mosquito doméstico tropical


Sequencing of Culex quinquefasciatus Establishes a Platform for Mosquito Comparative Genomics Science
Peter Arensburger, Karine Megy, Robert M. Waterhouse, Jenica Abrudan, Paolo Amedeo, Beatriz Antelo, Lyric Bartholomay, Shelby Bidwell, Elisabet Caler, Francisco Camara, Corey L. Campbell, Kathryn S. Campbell, Claudio Casola, Marta T. Castro, Ishwar Chandramouliswaran, Sinéad B. Chapman, Scott Christley, Javier Costas, Eric Eisenstadt, Cedric Feshotte, Claire Fraser-Liggett, Roderic Guigo, Brian Haas, Martin Hammond, Bill S. Hansson, Janet Hemingway, Sharon Hill, Clint Howarth, Rickard Ignell, Ryan C. Kennedy, Chinnappa D. Kodira, Neil F. Lobo, Chunhong Mao, George Mayhew, Kristin Michel, Akio Mori, Nannan Liu, Horacio Naveira, Vishvanath Nene, Nam Nguyen, Matthew D. Pearson, Ellen J. Pritham, Daniela Puiu, Yumin Qi, Hilary Ranson, Jose M. C. Ribeiro, Hugh M. Roberston, David W. Severson, Martin Shumway, Mario Stanke, Robert Strausberg, Cheng Sun, Granger Sutton, Zhijian (Jake) Tu, Jose Manuel C. Tubio, Maria F. Unger, Dana L. Vanlandingham, Albert J. Vilella, Owen White, Jared R. White, Charles S. Wondji, Jennifer Wortman, Evgeny M. Zdobnov, Bruce Birren, Bruce M. Christensen, Frank H. Collins, Anthony Cornel, George Dimopoulos, Linda I. Hannick, Stephen Higgs, Gregory C. Lanzaro, Daniel Lawson, Norman H. Lee, Marc A. T. Muskavitch, Alexander S. Raikhel, Peter W. Atkinson.

Pathogenomics of Culex quinquefasciatus and Meta-Analysis of Infection Responses to Diverse Pathogens Science
Lyric C. Bartholomay, Robert M. Waterhouse, George F. Mayhew, Corey L. Campbell, Kristin Michel, Zhen Zou, Jose L. Ramirez, Suchismita Das, Kanwal Alvarez, Peter Arensburger, Bart Bryant, Sinead B. Chapman, Yuemei Dong, Sara M. Erickson, S. H. P. Parakrama Karunaratne, Vladimir Kokoza, Chinnappa D. Kodira, Patricia Pignatelli, Sang Woon Shin, Dana L. Vanlandingham, Peter W. Atkinson, Bruce Birren, George K. Christophides, Rollie J. Clem, Janet Hemingway, Stephen Higgs, Karine Megy, Hilary Ranson, Evgeny M. Zdobnov, Alexander S. Raikhel, Bruce M. Christensen, George Dimopoulos, Marc A. T. Muskavitch.

Culex Genome White Paper261.13 KB
Culex Genome Project308.4 KB