Evolutionary dynamics of immune-related genes and pathways in disease vector mosquitoes

The genes that make up the immune system of the Aedes aegypti mosquito which transmits deadly viral diseases to humans have been identified in new research in Science.

The immune system of this mosquito is of great importance as scientists believe it plays a key role in controlling the transmission of viruses that cause yellow and dengue fevers – diseases that infect over 50 million people worldwide every year.

This study is the first of its kind on the newly-sequenced genome of the Aedes aegypti mosquito, which is also published in this week’s Science. The researchers identified over 350 genes which are involved in the Aedes mosquito’s immune system, and discovered that they evolve much faster than the rest of the genes in the genome. Identifying which of these key genes are implicated in the transmission of viral diseases is an area of future research that could lead to new ways of combating these diseases. One possibility would be to affect the activity of the genes and therefore help the mosquitoes fight off the viruses more effectively, preventing transmission to humans.

Imperial College scientists participating in this study established previously that other mosquitoes do have a robust immune system that can either allow or block transmission of malaria parasites. Further research will be needed to ascertain whether some of the newly discovered genes in Aedes may provide a similar defence mechanism that can fight the disease viruses.

Dr George Christophides of Imperial’s Division of Cell and Molecular Biology, senior author on the paper explains: “Our study has revealed the genetic ‘landscape’ made by parts of this mosquito’s newly-sequenced genome which are involved with immunity. By working to understand as much as possible about these genes, and the way they interact with specific pathogens, we hope to gain a more complete understanding of the mechanisms by which a pathogen either survives inside the insect body, or is killed by the insect’s defences.”

The international research team, led by Imperial PhD student Robert Waterhouse, focused on comparing the immunity genes of the Aedes mosquito with similar groups of genes in the harmless fruit fly and the Anopheles mosquito that transmits malaria. When comparing the two different mosquitoes, the scientists found some similarities in the genes controlling their respective immune systems, but also numerous differences. The team aims to discover which of these genetic differences could explain why one type of mosquito transmits dengue and yellow fevers, while the other transmits malaria. Beyond the present descriptive work, functional studies will be needed to clarify exactly how this happens.

“This study made us realise that the immune systems of insects are not static but evolve and differentiate rapidly, most likely in response to the different pathogens which each insect species encounters”, says Dr Christophides.

Professor Fotis Kafatos, senior researcher of Imperial’s immunogenomics lab and co-author of the paper, explains the significance of their study, saying: “Understanding the genetics behind pathogen/immune system interactions in disease vector mosquitoes may help us understand why, for example, some types of mosquitoes can transmit a particular human pathogen while others cannot. If those that cannot have evolved an effective immune system that fights off the pathogen, we may be able to use this knowledge to enhance specific reactions of the immune systems in other mosquitoes to control the spread of the disease.”

1. “Evolutionary dynamics of immune-related genes and pathways in disease vector mosquitoes”, Science, 22 June 2007.

Robert M. Waterhouse (1), Evgenia V. Kriventseva (2,3), Stephan Meister (1), ZhiYong Xi (4), Kanwal S. Alvarez (5), Lyric C. Bartholomay (6), Carolina Barillas-Mury (7), Guowu Bian (5), Stephanie Blandin (8), Bruce M. Christensen (9), Yuemei Dong (4), Haobo Jiang (10), Michael R. Kanost (11), Anastasios C. Koutsos (1), Elena A. Levashina (8), Jianyong Li, (12), Petros Ligoxygakis (13), Robert M. MacCallum (1), George F. Mayhew (9), Antonio Mendes (1), Kristin Michel (1), Mike A. Osta (1), Susan Paskewitz (14), Sang Woon Shin (5), Dina Vlachou (1), Lihui Wang (13), Weiqi Wei (15,16), Liangbiao Zheng (15,17), Zhen Zou (10), David W. Severson (18), Alexander S. Raikhel (5), Fotis C. Kafatos (1), George Dimopoulos (4), Evgeny M. Zdobnov (3,19,1), George K. Christophides (1).

(1) Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK.
(2) Department of Structural Biology and Bioinformatics, University of Geneva Medical School, 1211 Geneva, Switzerland.
(3) Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
(4) Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
(5) Department of Entomology and the Institute for Integrative Genome Biology, University of California, Riverside, California 92521, USA.
(6) Department of Entomology, Iowa State University, Ames, IA 50011, USA.
(7) Laboratory of Malaria and Vector Research, Twinbrook III Facility, NIAID, NIH, USA.
(8) UPR 9022 du CNRS, Avenir-Inserm, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
(9) Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, Madison WI 53706, USA.
(10) Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, OK 74078, USA.
(11) Department of Biochemistry, Kansas State University, Manhattan, KS 66506, USA.
(12) Department of Biochemistry, Virginia Tech, Blacksburg, USA.
(13) Department of Biochemistry, University of Oxford, Oxford, UK.
(14) Russell Labs, Department of Entomology, Madison, USA.
(15) Yale University School of Medicine, Epidemiology and Public Health, New Haven, USA.
(16) Fujian Center for Prevention and Control of Occupational Disease and Chemical Poisoning, Fujian, China.
(17) Institute of Plant Physiology and Ecology, Shanghai, China.
(18) Department of Biological Sciences, Center for Global Health and Infectious Diseases, University of Notre Dame, Notre Dame, IN 46556, USA.
(19) Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland.

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