The Genetic Basis of Host Preference and Resting Behavior in the Major African Malaria Vector, Anopheles arabiensis

We recently published the first study to report a genetic component to host choice behavior in the major malaria vector Anopheles arabiensis. In a collaboration with the University of California Davis, University of Glasgow, and the Environmental Health and Ecological Sciences Group, Ifakara Health Institute, Ifakara, United Republic of Tanzania, we assess the genetic basis for An. arabiensis host choice and resting behavior. We link human-fed behavior to allelic variation between the 3Ra inversion states. This effort was led by researchers at UC Davis, including Bradley Main, Yoosook Lee, Travis Collier, Anthony Cornel, Catelyn Nieman, Allison Weakley, and Gregory Lanzaro. Eleazar Eskin and Eun Yong Kang contributed data analysis and interpretation.

Mosquitoes that feed on human blood pose an enormous public health threat by transmitting numerous pathogens, such as dengue virus, Zika virus, and malaria. Together, these mosquito-borne diseases kill more than one million people per year. Human exposure to malaria is driven by variable mosquito behaviors such as: (1) propensity to feed on humans relative to other animals (anthropophily) and (2) preference for living in close proximity to humans, as reflected by biting and residing inside houses (endophily).

Our project focused on the potential for An. arabiensis, the only remaining malaria vector in many parts of Africa, to adapt its behavior to avoid control measures such as insecticide-treated nets and indoor residual sprays. To investigate the genetic basis of host choice and resting behavior, we sequenced the genomes of 23 human-fed and 25 cattle-fed mosquitoes collected both in-doors and out-doors in the Kilombero Valley, Tanzania. We tested for genetic associations with each of the four phenotypes: human-fed, cow-fed, resting indoors, and resting outdoors.

With these genomes, we identified a set of 4,820,851 segregating SNPs after imposing a minor allele frequency threshold of 10%. We estimated the genetic component (or “SNP heritability”) for each phenotype. Results suggest a genetic component for host choice and no genetic component for resting behavior.

To test for the existence of genetic structure within our set of 48 sequenced genomes, individuals were partitioned by genetic relatedness using a Principle Component Analysis (Genome-Wide Complex Trait Analysis software, GCTA) applied to all SNPs. Using this approach, we observed three discrete genetic clusters. We used a novel population-scale inversion genotyping method to identify an association between the standard arrangement of 3Ra (3R+) and cattle-fed An. arabiensis. We highlight two intriguing candidate genes within the 3Ra, including the odorant binding protein Obp5, and the odorant receptor Or65. The enrichment of 3R+ among cattle-fed mosquitoes provides support for a genetic component to host choice, which is consistent with the report that zoophily can be selected for.

Genetic variation explained by the 2Rb and 3Ra inversions. For more information, see our paper.

Our multiplex genotyping assays allowed us to directly estimate relationships between host choice and genotype in wild mosquitoes in a high-throughput and economical fashion. Given the importance of mosquito feeding and resting behavior to the effectiveness of malaria control and transmission, there is an urgent need to understand the underlying biological determinants of these behaviors and their short- and long-term impact on the effectiveness of current public health interventions.

For more information, see our paper, which is available for download through PLoS Genetics:

The full citation to our paper is:
Main, B.J., Lee, Y., Ferguson, H.M., Kreppel, K.S., Kihonda, A., Govella, N.J., Collier, T.C., Cornel, A.J., Eskin, E., Kang, E.Y. and Nieman, C.C., 2016. The Genetic Basis of Host Preference and Resting Behavior in the Major African Malaria Vector, Anopheles arabiensis. PLoS Genet, 12(9), p.e1006303.