A new gene that determines the sex of malaria mosquitoes has been discovered by scientists at The Pirbright Institute. The gene, named femaleless by the researchers, can be manipulated to prevent female mosquitoes from developing (only females bite to feed on blood and spread disease), which could provide a new means for genetic control of mosquito populations that could be used to break malaria transmission.
In a study published in Current Biology, scientists from the Vector Molecular Biology Group initially identified femaleless in the mosquito Anopheles gambiae, a primary carrier of malaria in Africa. They demonstrated that if the expression of the gene in mosquito eggs is experimentally decreased, females develop into individuals that look more like males in appearance and are unable to mate or feed on blood, or their development is arrested altogether.
Further investigation established that femaleless is exclusive to mosquito species belonging to the genus Anopheles, which is solely responsible for transmitting human malaria. In 2019 alone, malaria caused over 200 million clinical cases and more than 400,000 deaths globally. The gene was detected in all Anopheles species studied, and its genetic sequence proved to be highly conserved (similar in different species). The study also demonstrated that disabling femaleless in distantly related Anopheles species has the same effect as seen in Anopheles gambiae.
The researchers also found that femaleless, in addition to the sex determining role in developing females, is involved in controlling a phenomenon called dosage compensation. Like in humans, females of the Anopheles mosquitoes have a pair of identical sex chromosomes, called XX, whilst males have XY. Dosage compensation is a process in which expression levels of genes from a single X chromosome in males are two-fold increased, to equal the levels of expression from the two X chromosomes in females.
Inactivating femaleless causes the genes from both X chromosomes in females to express at twice the normal rate, which is toxic to female mosquitoes. This is only the second time the identity of the molecular link between sex determination and dosage compensation in insects has been discovered, the first being found in the common fruit fly, Drosophila melanogaster.
Dr Jaroslaw Krzywinski, head of the Vector Molecular Biology Group at Pirbright said: “We first investigated femaleless because we suspected it would have a role in sex determination, but it was unexpected that knockdown of the gene’s expression would lead to female lethality. This gene is highly conserved in sequence and function in various Anopheles species and, as such, provides an excellent universal target to eliminate females of major malaria vector species, enabling the control of their populations. We hope that this discovery could help us to tackle one of the most devastating insect-borne diseases in the world.”
Notes to editors
The paper femaleless controls sex determination and dosage compensation pathways in females of the Anopheles mosquitoes is available on the Current Biology website at: https://www.cell.com/current-biology/fulltext/S0960-9822(20)31834-0
This study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI).
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About The Pirbright Institute
The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) part of UK Research and Innovation (UKRI), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.
The Institute is an independent company, limited by guarantee and a registered charity, governed by a Board of non-executive Trustee Directors.
With an annual income of £35 million from grants and commercial activity, and a total of £25.2 million strategic investment from BBSRC UKRI during 2019-2020, the Institute contributes to global food security and health, improving quality of life for animals and people.
For more information about The Pirbright Institute see: www.pirbright.ac.uk
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