By Iqbal Pittalwala, (951) 827-6050, iqbal@ucr.edu, UC Riverside
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Culex quinquefasciatus taking a blood meal. (Photo by Anton Cornel) |
UC Riverside researchers spearheaded the multiyear project that could result in novel strategies to fight West Nile and other Culex-transmitted diseases.
RIVERSIDE— Last year, 720 people in the United States became infected with West Nile virus, a potentially serious illness that is spread through the bite of a mosquito — the Culex mosquito — that has first fed on infected birds. Such mosquitoes have the virus eventually located in their salivary glands and transmit the disease to humans and animals when they bite to draw blood.
To understand the genetic makeup of the Culex mosquito and how the insect is able to transmit this and other viruses, an international team of scientists, led by geneticists at the University of California, Riverside, has sequenced the genome of Culex quinquefasciatus, a representative of the Culex genus (or group) of mosquitoes.
A close study of the genome, the researchers say, could give scientists the clues they need to target specific Culex genes that are involved in the transmission of West Nile virus, St. Louis encephalitis, lymphatic filariasis and other diseases spread by the Culex group of mosquitoes. Knowledge of such genes would be an important step in developing strategies to combat the spread of these pathogens.
The genomes of Anopheles gambiae (which transmits malaria) and Aedes aegypti (which transmits yellow fever and dengue) were published in 2002 and 2007, respectively. Now, with the sequencing of Culex quinquefasciatus, scientists have completed the triangulation of entire genome sequences of three genera of mosquitoes that are the main vectors of deadly human diseases, and will have access to representative genomes from the three mosquito groups.
“We can now compare and contrast all three mosquito genomes, and identify not only their common genes but also what is unique to each mosquito,” said Peter Arensburger, an assistant research entomologist in the Center for Disease Vector Research and the Department of Entomology, who led the substantial bioinformatics component of the multiyear research effort. “Moreover, now that we have sequenced the Culex genome, we can begin to identify which mosquito genes get turned on or turned off in response to infection — knowledge that is critical to developing strategies for preventing the transmission of West Nile virus and other disease vectors.”
Study results appear in the Oct. 1 issue of Science.
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Dengue mosquito, Aedes egypti. (Photo by James Gathany, CDC) |
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| Malaria mosquito, Anopheles gambiae. (Photo by Anton Cornel) |
The researchers report that C. quinquefasciatus, also known as the southern house mosquito, has a genome size of 579 million nucleotides, which is intermediate between the genome sizes of Anopheles gambiae (278 million nucleotides) and Aedes aegypti (about 1,380 million nucleotides). However, C. quinquefasciatus has a higher number of genes (18,883 genes) than Anopheles gambiae (12,457 genes) or Aedes aegypti (15,419 genes).
“We do not know why this is the case,” said Arensburger. “Culex quinquefasciatus is very widely distributed throughout the globe; the same species is found in California and South Africa. It is possible that the large number of genes in this mosquito helped it survive in a wide variety of habitats.”
The researchers also report that the genome for C. quinquefasciatus bears more similarity to the Aedes aegypti genome than the Anopheles gambiae genome.
Thirty-seven institutions collaborated with UC Riverside on the research project that began in 2004. Besides Arensburger, the UC Riverside team includes Peter Atkinson, the director of the Center for Disease Vector Research and a professor of entomology, and Alexander Raikhel, a distinguished professor of entomology.
“We coordinated with researchers around the world to accomplish the sequencing of the Culex genome,” said Atkinson, the senior author of the study and the principal investigator of the grants that funded UC Riverside’s contribution to the research. “We could not have done this without the outstanding computing support we received from UC Riverside’s Institute for Integrative Genome Biology. It enabled us to perform vast and complex analyses here on campus, and gave us the confidence to get the project going and completed.”
With more than 1,200 described species, Culex is the most diverse and geographically widespread of the three mosquito genera. The adult mosquito measures 4-10 millimeters. Only females spread disease. Culex-transmitted diseases, such as West Nile virus, are difficult to eradicate because birds and animals the mosquito feeds on are mobile, capable of spreading disease quickly over large areas.
West Nile virus first appeared in the United States in the summer of 1999. Since then it has been found in all 48 contiguous states.
The research paper in Science is accompanied by a second paper, led by researchers at Boston College, Mass., and Iowa State University, that focuses on a set of immune genes in C. quinquefasciatus. The paper explores why some of these genes are “upregulated” (show an increase in gene expression) while others are “downregulated” in response to pathogens. Arensburger, Atkinson and Raikhel are coauthors on the companion paper in the same issue of Science on Culex immunobiology with Raikhel’s laboratory contributing significantly to this work.
With the sequencing of the C. quinquefasciatus genome completed, UC Riverside researchers will focus next on genes of particular interest to efforts aimed at preventing the spread of human diseases by these mosquitoes.
Grants from the National Institutes of Health supported UC Riverside’s contribution to the research.
The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UC Riverside's enrollment of over 19,000 is expected to grow to 21,000 students by 2020. The campus is planning a medical school and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Graduate Center. The campus has an annual statewide economic impact of more than $1 billion. -- By Iqbal Pittalwala, UC Riverside
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| UC Davis mosquito researcher Anthony "Anton" Cornel. He collected and established the colony of Culex quinquefasciatus mosquitoes that was sequenced. Here he works in a field tent identifying mosquitoes In the forest of N'Dibi in Cameroon. (Photo by Kevin N'Gabo) |
UC Davis Scientists Collaborate in Genome-Sequencing Research
Several University of California, Davis researchers contributed to the international research led by UC Riverside geneticists that resulted in a major milestone: the sequencing of the genome of Culex quinquefasciatus, the so-called “southern house mosquito.”
The research, launched in 2004 and published in the Oct. 1, 2010 edition of Science, involved scientists from 38 institutions. Culex mosquitoes transmit the West Nile virus, St. Louis encephalitis, lymphatic filariasis and other diseases.
UC Davis mosquito researchers Anthony “Anton” Cornel and Gregory Lanzaro co-authored the research paper. Scientists in the Bruce Hammock and Walter Leal labs also participated in the research.
Cornel collected and established the mosquito colony that was sequenced.. Cornel is an associate professor of entomology at UC Davis who directs the mosquito research lab at the UC Kearney Agricultural Center, Parlier.
“We have multiple sub colonies of the Johannesburg colony now established in numerous insectaries worldwide,” said Cornel.
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Mosquito researcher Greg Lanzaro |
Lanzaro, a longtime collaborator with Cornel, is a professor in the School of Veterinary Medicine and former director of the UC Mosquito Research Program and the Center for Vectorborne Diseases. Both Cornel and Lanzaro serve as graduate student advisors in the UC Davis Department of Entomology.
The Hammock lab played a role in annotating and examining divergence of esterases and glutathione-S tranferases in this mosquito. Bruce Hammock is a distinguished professor of entomology. The lab of Walter Leal, professor of entomology, added expertise in chemical ecology.
Cornel hailed the research as “another milestone in mosquito genomics—we now have a full genome sequence of a third medically important mosquito, Culex quinquefasciatus.”
“This is the first species within the Culex genus fully sequenced and now offers many opportunities for research on comparative genomics and post genomics between three mosquito species now fully sequenced—namely the major malaria vector, Anopheles gambiae; the major dengue virus vector, Aedes aegypti; and a major vector of West Nile virus, Culex quinquefasciatus.”
The genome of Culex is much larger than the other two species--52 percent more than Anopheles gambiae and 22 percent more than Aedes aegypti, Cornel said. “Research on these three mosquitoes--how they find their hosts and vector diseases and the mechanisms involved--will likely blossom in the near future.”
The Leal lab played an important chemical-ecology role. “About 10 years ago we isolated the first olfactory protein from a mosquito species, the odorant-binding protein-1 from the southern house mosquito,” Leal said. “It was after months of hard work and having had to extract more than 1,000 antennae.”
A year ago, with the advent of the Culex genome, researcher Julien Pelletier of the Leal lab identified the complete repertoire of odorant-binding proteins from this species, which includes 53 OBPs. “He also identified 139 odorant receptors, two of which we have already de-orphanized,” Leal said. “We are now poised to use these olfactory proteins as molecular targets for the development of better oviposition attractants and design new environmentally friendly and sustainable strategies for monitoring and controlling mosquito populations. “--Kathy Keatley Garvey, UC Davis Department of Entomology |
--Kathy Keatley Garvey
Communications specialist
UC Davis Department of Entomology
(530) 754-6894
