Genomics of

African Malaria Vectors

Nora J. Besansky       Professor Ph.D., Yale University Postdoctoral, Centers for Disease Control

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My research focuses primarily on African vectors of human malaria: the anopheline mosquitoes known as Anopheles gambiae and Anopheles funestus. 

                  

Left, An. gambiae; right, An. funestus.  Photos courtesy of J. Gathany, CDC

By examining patterns of genetic variation across species, populations, and different regions of the genome, inferences can be made about phylogenetic relationships, population structure and history, speciation and adaptive change.  These themes run through various lines of investigation pursued in my laboratory, often in collaboration with other scientists in Europe and Africa.  Past and present projects have included transposable element discovery, molecular genetics of the An. gambiae Y chromosome, characterization of chromosomal inversion breakpoints, ecological genomics of chromosomal inversions, population genetic structure, comparative genomics, genetics of emerging species, semipermeable species boundaries, and molecular systematics of anophelines.  The common thread to this research is the question, “What makes a good vector?”

 

The context of this research is the problem of human malaria, a major cause of unimaginable suffering in developing countries of the tropics-- particularly those in subSaharan Africa.  Each year, an estimated 3 million children under the age of five die from this disease, despite the fact that it is treatable.  The enormity of the death toll has been likened to seven jumbo jets crashing in Africa on a daily basis.  There are numerous factors contributing to this public health crisis: the tropical climate, extreme poverty, physical isolation, malnutrition, lack of access to healthcare, a predominately rural population, and the burden of government debt (please see Sachs, “The End of Poverty”).  However, the feature that sets Africa apart in the intensity of malaria transmission and the challenge of interrupting it are its mosquito vectors, which prefer human hosts above all else.  For human malaria to be transmitted, a mosquito infected from biting one person with malaria must take her next blood meal from another person, and this sequence is virtually guaranteed by An. gambiae and An. funestus, the two most anthropophilic anopheline mosquitoes in the world.  They happen to live in Africa, explaining why Africa suffers 90% of all malaria deaths. 

 

What makes them such good vectors when hundreds of other anopheline mosquitoes are not medically important?  Clearly, one feature is their association with humans, as reflected in a strong preference for human blood and the exploitation of anthropogenic settings for larval development and adult shelter.  A second feature, not as immediately obvious at first glance, is their abundance and widespread distribution across many diverse ecological settings of subSaharan Africa.  This distribution reflects a powerful genetic flexibility.  When it is considered that these species are closely tied to humans, whose population started to rise significantly only following the agricultural revolution, it can be inferred that they have not merely adapted, but have adapted quite rapidly to a broad array of different environments.  Current research in my laboratory aims to understand the genetic basis of these adaptations, and their consequences in terms of population structure and speciation.

 

The example of emerging species within An. gambiae known as M and S forms illustrates this problem and emphasizes its public health relevance.  The “classic” breeding site utilized by An. gambiae is a small temporary bare-edged pool or puddle exposed to full sun-light.  Such sites, as might be created by a footprint or tire track, are rain-dependent.  Accordingly, when the dry season comes, An. gambiae breeding should cease along with malaria transmission by this species.  This situation applies to East Africa, the exclusive domain of the S form of An. gambiae.  However, in West Africa, genetically and behaviorally divergent populations of An. gambiae known as the M form, coexisting with the S form, have evolved the ability to exploit semi-permanent or permanent breeding sites characterized by the impoundment of water for agricultural irrigation.  Prime among these are ricefields.  Because they are irrigated, ricefields are available for breeding by the M form during the dry season and also in geographic zones that are too arid to sustain this species under natural conditions.  Thus, the M form remains reproductively active in environments that exclude the S form, and with emergence of the M form has come increased malaria transmission both temporally and spatially.  The ecological divergence of M and S forms has been accompanied by at least partial reproductive isolation.  Nor is this situation unique in Africa.  Together with collaborators, we recently uncovered a parallel phenomenon occurring in An. funestus.  Current research ongoing in my laboratory aims at understanding the genetic basis of differential adaptation and behavioral barriers to mating that have developed between incipient species.  Elucidation of this phenomenon bears on understanding the speciation process, and can offer insights into how vector populations are structured in Africa as well as providing potential new genetic targets for vector control. 

 

The application of this research to malaria control is far from immediate.  Practical on-the-ground solutions such as bed nets and insecticides are needed now, while research into novel sustainable genetic approaches continues.  Eventual control or elimination of this disease is possible, but will take a concerted international effort and a multi-pronged if not multidisciplinary approach.