NEW YORK (GenomeWeb) – A University of California, Davis-led team of researchers has found that certain malaria-transmitting mosquitos that tend to feed on humans harbor a particular chromosomal rearrangement.
The team collected Anopheles arabiensis mosquitos, which remain the dominant transmitters of malaria in many parts of Africa, from three villages in Tanzania for sequencing. Some mosquitos were trapped indoors, while others were caught outdoors, and some had fed on cattle, others on humans, and some on other animals. As reported today in PLOS Genetics, mosquitos that fed on cattle were more likely to have the presumed ancestral form of the 3Ra chromosomal inversion.
"Whether there is a genetic basis to feeding preferences in mosquitos has long been debated," first author Bradley Main, a researcher at the UC Davis School of Veterinary Medicine, said in a statement. "Using a population genomics approach, we have established an association between human feeding and a specific chromosomal rearrangement in the major East African malaria vector. This work paves the way for identifying specific genes that affect this critically important trait."
While treated nets and indoor insecticide use have reduced the numbers of some malaria vectors, An. arabiensis, which has a broader host range, has been less affected by those approaches. Better understanding how An. arabiensis chooses its host could inform disease control efforts, the researchers added, as mosquitos that feed on cattle are less likely to transmit malaria among people.
Main and his colleagues collected mosquitos from indoor and outdoor spots in three southeastern Tanzanian villages — Lupiro, Minepa, and Sagamaganga — during a period of two years. They then analyzed blood meals from 1,731 female An. arabiensis they collected and, using a multiplex genotyping assay, identified what species they had fed upon.
In addition, using a generalized linear mixed model approach, they found that the presence of livestock was inversely correlated with the number of human-fed mosquitos, while being trapped indoors was positively associated with the frequency of human feeding.
They sequenced 48 An. arabiensis individuals — 25 that had fed on cattle and 23 that had fed on humans — to a median depth of 18X. Twenty-four of the mosquitos had been collected outside and 24 inside. From this, they identified some 4.8 million segregating SNPs.
They used the data they collected to estimate SNP heritability for feeding on people or on cattle and for resting inside or outside. Host choice, they reported, appeared to be heritable, while resting location was not.
A principal components analysis based on the SNP data clustered them into three groups, based largely on what combination of 3Ra and 2Rb chromosome inversion states they had.
After developing an inversion genotyping assay, Main and his colleagues genotyped 363 blood-fed female mosquitos collected in Lupiro. About a third of the mosquitos had fed on humans while another third had fed on cattle. They found an enrichment of the standard arrangement of 3Ra among cattle-fed versus non-cattle-fed mosquitos.
The researchers homed in on two candidate genes in the 3Ra region: the odorant binding protein Obp5, which is expressed in female antennae and thus could be involved in host-seeking, and the odorant receptor Or65, in which they noted allelic variation between inversion arrangements. Controlled host preference assays testing various genotypes are now needed to gauge any link between these candidates and host choice, they added.
"A better understanding of the genetic basis for host choice in An. arabiensis may also improve vector control if cattle-biting mosquitos can be genetically engineered and released in the population, having an effect similar in concept to zooprophylaxis," or the diversion of disease vectors away from human hosts to other hosts, Main and his colleagues wrote in their paper.