Scientists methodically identify genes related to blood feeding and non-biting mosquitoes

Researchers have taken the first step on a path that eventually could result in female mosquitoes that no longer bite and spread diseases.

A group of scientists at the University of Birmingham, University of Oregon, Oregon Health and Science University, University of Notre Dame, and The Ohio State University methodically identified 902 genes related to blood feeding and 478 genes linked to non-blood feeding from the mosquito Wyeomyia smithii.

The species, commonly known as pitcher plant mosquitoes, is found in swamps and bogs along the east coast of North America from north Florida into Canada. The species completes its pre-adult life cycle in the water of pitcher plants.

The method used to isolate genes in this research, published in Proceedings of the National Academy of Sciences, will now be used in other species with a goal to isolate universal non-biting genes across multiple diseases.

Professor John Colbourne, of the School of Biosciences at the University of Birmingham, said: "The spread of blood-borne diseases by mosquitoes relies on their taking a blood meal; if there is no bite, there is no disease transmission.

"Our research is important as it provides a unique starting point to determine if there are universal nonbiting genes in mosquitoes that could be manipulated as a means to control vector-borne disease."

The next species to come under focus will be: common house mosquitoes (Culex pipiens), which spread many encephalitis diseases, West Nile virus and heartworm; Asian tiger mosquitoes (Aedes albopictus), which is spreading rapidly in the United States and carries, among other viruses, dengue, Zika and yellow fever; and the African malaria mosquito Anopheles gambiae.

Dr William Bradshaw, of the University of Oregon, said: "We'll see what comparable genes pop out of these other species and identify commonalities.

"We will continue this process, the end point of which will be the identification of universal non-biting mosquito genes."

This could provide pharmaceutical targets for non-toxic inhibitors that could be developed to turn off biting genes but also allow mosquito populations to thrive and keep their place in the food chain, the researchers said.

Dr Chrisrina Holzapfel, also of the University of Oregon, added: "We are seeking the genes that are in the transition between biting and non-biting.

"The reason we are seeking those genes is because if we can figure out how to incapacitate biting genes, that would mitigate vector-borne disease worldwide. If there is no bite, there is no disease transmission, period."

The research initially targeted Wyeomyia smithii because it is the only known species to have females that bite to obtain blood and are obligate non-biters - those that don't seek blood. The researchers said that they had realized the possibility 20 years ago that genes guiding these lifestyle differences existed and had evolved in nature, but the technology was not yet developed to isolate these genes.

Females are the blood-feeders in mosquito populations and, thus, the vectors of diseases; males feed on nectar.

In the project, funded by two National Science Foundation grants, the research team examined 21,618 potential genes in the pitcher plant mosquito under a selection experiment conducted in a laboratory for more than seven generations. By comparing genes that change with the biting behavior with those from natural populations that either bite or don't bite, they identified and extracted 1,380 genes that were determined to have direct effects on differentiating the biting and non-biting lifestyles.

The step-by-step method involved strong, directional gene selection on a low-biting Florida population. By saving and mating only females about to blood-feed, researchers created an avid, voracious biting line. A group of disinterested non-biters also was developed from the same population by eliminating all females that bit or attempted to bite.

The research team also examined known metabolic pathways of the isolated genes - knowledge that, when further understood, will be helpful for future efforts by pharmaceutical companies to harness a control approach that nature already has established.

Professor Michael Pfrender, director of the Genomics & Bioinformatics Core Facility at the University of Notre Dame, added: "This study shows the power of combining well-designed breeding experiments and genomics data to gain insights into the biology of disease vectors."