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International Team Sequences Genome of West Nile-Transmitting Mosquito

By Andrea Anderson

NEW YORK (GenomeWeb News) – A pair of papers appearing online today in Science are providing insights into the genomics and pathogenomics of a mosquito species that spreads West Nile virus and other pathogens.

An international research team led by investigators at the University of California at Riverside reported that they have sequenced the genome of the southern house mosquito, Culex quinquefasciatus, the third mosquito to be sequenced so far. The work — which is already being used by those interested in mosquito vector-mediated disease transmission — is expected to spur additional studies in a range of related areas.

The value of the project is that it will provide researchers around the world who are interested in Culex and how it transmits pathogens with information that could address specific research questions, senior author Peter Atkinson, director of the University of California at Riverside's Center for Disease Vector Research, told GenomeWeb Daily News.

Previous mosquito genome sequencing studies focused on Anopheles gambiae and Aedes aegypti species, mosquitoes that transmit malaria and yellow and dengue fevers, respectively.

For the latest mosquito sequencing study, Atkinson and colleagues focused on C. quinquefasciatus — one of more than 1,200 species from the Culex genus.

Understanding Culex genetics has implications both for basic biology and human health, the researchers explained, since mosquitoes in the genus can transmit West Nile virus as well as the pathogens causing St. Louis encephalitis, lymphatic filariasis (also known as elephantiasis), and other diseases.

The team of investigators from dozens of research institutions primarily used Sanger sequencing to tackle the 579 million base genome of C. quinquefasciatus, Atkinson said, focusing on a strain isolated from a South African pond that represents one end of a Culex species complex spectrum.

During their annotation and analyses of the genome, the researchers identified 18,883 genes in the southern house mosquito — nearly twice as many as previously reported in the smaller A. gambiae genome and about 22 percent more than in the much larger A. aegypti genome.

"When we first saw this expanded gene number we were actually very surprised and very worried," Atkinson said, explaining that the mosquito's hefty gene inventory prompted the team to perform additional manual and automatic annotation steps.

Once convinced that the annotation was accurate, the team turned their attention to the types of gene families that have been enlarged in the southern house mosquito — and potential explanations for these expansions.

For instance, they found that gene families involved in scent and taste reception, and immune-related processes were among those that had undergone expansions in C. quinquefasciatus, fueling speculation that these expansions may contribute to the mosquito species' ability to survive on every continent except Antarctica, feeding on a variety of hosts.

"It's cosmopolitan. It's found around the world in many different environments and it has a wide host range," Atkinson explained. "Maybe if you're talking about its ability to find different hosts — such as how it uses olfactory cues — you can come up with scenarios that might explain some of these gene expansions."

Even so, more research is needed to explore this in more detail, he added. "It's difficult to prove. It's just speculation."

With the southern house mosquito genome in hand, the team plans to further explore the bases of disease transmission in mosquitoes in the hopes of finding clues for preventing or treating mosquito-born illnesses.

"[N]ow 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," lead author Peter Arensburger, an entomologist with the University of California, Riverside's Center for Disease Vector Research, said in a statement.

Indeed, researchers from the US, UK, Switzerland, and Sri Lanka — including Atkinson, Arensburger, and other members of the sequencing team — reported in a second Science paper that they have already started applying information in the newly sequenced genome to investigate mosquito immune response to pathogens.

That researchers used whole-genome microarrays to look at the sorts of genes that are up- and down-regulated in C. quinquefasciatus and other mosquitoes in response to bacterial, eukaryotic, and viral pathogens, including West Nile virus.

Comparisons between all three sequenced mosquito species showed that immune-related gene families have undergone expansion in the southern house mosquito compared to the other two species.

"Because Culex is such a good vector of many pathogens … it's perhaps not surprising that the immune response genes have undergone something of an expansion," Atkinson noted. "You can imagine if you look back over evolutionary time in the ancestors of Culex, the stresses that insect must have been under as a vector of so many pathogens would have been pretty impressive."

Even so, based on their assessment of more than two-dozen mosquito-pathogen combinations, the team concluded that many of the pathogens transmitted by mosquitoes have developed tricks allowing them to go largely undetected by mosquito immune systems.

"The pathogens are obviously under continual selective pressure to make sure that they are transmitted. There's a little war going on — a host-pathogen war — which enables these pathogens to survive," Atkinson said. "Insights into that ongoing conflict will come from these genome projects."

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