@article {Main044701, author = {Bradley J Main and Yoosook Lee and Heather M Ferguson and Katharina S Kreppel and Anicet Kihonda and Nicodem J Govella and Travis C Collier and Anthony J Cornel and Eleazar Eskin and Eun Yong Kang and Catelyn C Nieman and Allison M Weakley and Gregory C Lanzaro}, title = {The genetic basis of host choice and resting behavior in the major African malaria vector, Anopheles arabiensis}, elocation-id = {044701}, year = {2016}, doi = {10.1101/044701}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Malaria transmission is dependent on the propensity of Anopheles mosquitoes to bitehumans (anthropophily) instead of other dead end hosts. Recent increases in the usage of Long Lasting Insecticide Treated Nets (LLINs) in Africa have been associated with reductions in highly anthropophilic vectors such as Anopheles gambiae s.s.,leaving less anthropophilic species such as Anopheles arabiensis as the most prominent remaining source of transmission in many settings. An.arabiensis is more of a generalist in terms of its host choice and resting behavior, which may be due to phenotypic plasticity and/or segregating allelic variation. To investigate the potential genetic basis of host choice and resting behavior in An. arabiensis we performed a genome-wide association study on host choice (human-or cattle-fed) and resting position (collected indoors or outdoors) in the Kilombero Valley, Tanzania. This represents the first genomic/molecular analysis of host choice and resting behavior in a malaria vector. We identified a total of 4,820,851 SNPs, which were used to conduct the first genome-wide estimates of {\textquoteright}SNP heritability{\textquoteright} for host choice and resting behavior in this species. A genetic component was detected for host choice (human vs cow fed; permuted P = 0.002), but there was no evidence of a genetic component for resting behavior (indoors versus outside; permuted P = 0.465). A principal component analysis (PCA) segregated individuals based on genomic variation into three groups which are characterized by differences at the 2Rb and/or 3Ra paracentromeric chromosome inversions. There was a non-random distribution of cattle-fed mosquitoes between the PCA clusters, suggesting that alleles linked to the 2Rb and/or 3Ra inversions may influence host choice. Using a novel inversion genotyping assay, we detected a significant enrichment of the standard arrangement (non-inverted) of 3Ra among cattle-fed mosquitoes (N=129) versus all non-cattle-fed individuals (N=234; рез2, p=0.007). Thus, tracking the frequency of the 3Ra in An. arabiensis populations is important, especially in relation to the emergence of behavioral avoidance(e.g. shifting toward cattle-feeding) in some populations. A better understanding of the genetic basis for host choice in An. arabiensis may also open avenues for novel vector control strategies based on introducing genes for zoophily into wild mosquito populations.Author summary Malaria transmission is driven by the propensity for mosquito vectors to bite people, whilst its control depends on the tendency of mosquitoes to bite and rest in places where they will come into contact with insecticides. In many parts of Africa, Anopheles arabiensis is now the only remaining vec 63 tor in areas where coverage with Long Lasting Insecticide Treated Nets is high. We sought to assess the potential for An. arabiensis to adapt its behavior to avoid control measures by investigating the genetic basis for its host choice and resting behavior. Blood fed An. arabiensis were collected resting indoors and outdoors in the Kilombero Valley, Tanzania. We sequenced a total of 48 genomes representing 4 phenotypes (human or cow fed, resting in or outdoors) and tested for a genetic basis for each phenotype. Genomic analysis followed up by application of a novel molecular karyotyping assay revealed a relationship between An. arabiensis that fed on cattle and the standard arrangement of the 3Ra inversion. This indicates that the host choice behavior of An. arabiensis has has a substantial genetic component. Validation with controlled host preference assays comparing individuals with the standard and inverted arrangement of 3Ra is still needed.}, URL = {https://www.biorxiv.org/content/early/2016/06/07/044701}, eprint = {https://www.biorxiv.org/content/early/2016/06/07/044701.full.pdf}, journal = {bioRxiv} }