Mosquito genomes may hold the key to combating malaria
Malaria is one of the world's deadliest diseases, but cutting-edge research into the genetics of malaria-carrying mosquitoes could lead to new methods to prevent transmission that could save hundreds of thousands of lives worldwide.
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Of the around 500 species of Anopheles mosquito globally, only about two dozen transmit human malaria, suggesting genetic variations are responsible for determining why some types of anophelines are vectors of the disease and others are not.
Vectorial capacity varies greatly among even very closely-related mosquito species, making understanding what defines an effective malaria vector critical to developing successful disease control strategies, explains Robert Waterhouse, a computational evolutionary biologist at the Université de Genève.
From tormentors to research focus
Born in the landlocked African country of Swaziland and having twice contracted malaria as a child, Waterhouse has dedicated his scientific career to studying mosquitoes, which he describes as the tormentors of his childhood. His research has recently been advanced through the EU-funded ANOCAP project, in which he led the development and deployment of computational strategies to study multiple mosquito genomes.
The work, carried out between the Massachusetts Institute of Technology in the US and the Université de Genève in Switzerland, has led to extensive genomic data resources and improved understanding of the evolution of the genetic factors that influence how and why some anophelines carry and transmit malaria to humans.
We undertook the complete genome sequencing of multiple Anopheles mosquito species, using both laboratory colonies and wild-caught specimens to obtain genomic DNA and whole-body RNA, Waterhouse says.Importantly, these genomic resources sampled a range of evolutionary distances from Anopheles gambiae, the major African malaria vector species, a variety of geographic locations and ecological conditions, and varying degrees of vectorial capacity.
The ANOCAP team used novel computational tools to interrogate genomes for patterns of natural selection that shape the variety of functional genomic elements governing the biology of mosquitoes and other insects, including related species such as fruit flies.
A comparative analysis of 11 636 mosquito gene families, for example, indicated that the birth/death rate of genes in anophelines could be at least five times higher than for fruit flies.
As Waterhouse points out, such changes in gene family size may offer clues to understanding the functional diversification of anophelines over the past 100 million years. And by understanding how some types anophelines evolved to carry malaria, it should be possible to develop strategies to control their spread and hence transmission of the disease.
This remarkable dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts, Waterhouse explains. Many of the best successes of previous efforts to locally eliminate malaria have been accomplished wholly or in part through controlling the vector, thus, an improved understanding of the mosquitos biology is a key weapon in the continued fight against the disease.
Novel genomic resources and tools for the scientific community
The important genomic information resources generated by ANOCAP have been deposited at VectorBase, a National Institute of Allergy and Infectious Diseases bioinformatics resource centre that provides genomic, phenotypic and population-centric data to the scientific community for insects that carry human pathogens.
Waterhouse and other participants in the ANOCAP project are continuing to work together on studying and expanding the data, including through the manual curation of gene models using VectorBase online tools. In addition, the computational strategies developed in ANOCAP are also being used to study the genomes of Asian tiger mosquitoes, bed bugs, bees, sheep blowflies and other species that have an impact on human health and agriculture.
Waterhouse has been building on the success of ANOCAP, which was funded through a Marie Skłodowska-Curie fellowship grant. He has since launched a comprehensive biocuration training programme for arthropod genomics at several universities in South Africa.
The programme, supported by a micro-grant from the International Society for Biocuration and a crowd-funding campaign, is providing junior researchers and students with a comprehensive grounding in the principles of genomics approaches to studying insects that are particularly important because of their effects on humans, livestock and crops.
With new data resources, computational tools and improved genomics training, the ANOCAP project has generated multiple opportunities for the development of innovative approaches to tackle insect-borne diseases that impact global health issues.