TY - JOUR T1 - The genetic basis of host preference and indoor resting behavior in the major African malaria vector, <em>Anopheles arabiensis</em> JF - bioRxiv DO - 10.1101/044701 SP - 044701 AU - Bradley J Main AU - Yoosook Lee AU - Heather M Ferguson AU - Anicet Kihonda AU - Nicodem J Govella AU - Katharina S Kreppel AU - Travis C Collier AU - Anthony J Cornel AU - Eleazar Eskin AU - Eun Yong Kang AU - Catelyn C Nieman AU - Allison M Weakley AU - Gregory C Lanzaro Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/04/05/044701.abstract N2 - Malaria transmission is dependent on the propensity of Anopheles mosquitoes to bite humans (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 more zoophilic species such as Anopheles arabiensis as the most prominent remaining source of transmission in many settings. An. arabiensis appears to be more of a generalist in terms of host preference and resting behavior, which may be due to phenotypic plasticity or segregating allelic variation. To investigate the genetic basis of host preference and resting behavior in An. arabiensis we sequenced and analyzed genomes of 48 human- or cattle-fed An. arabiensis that were captured resting indoors or outdoors in a village in the Kilombero Valley, Tanzania. A total of 4,820,851 SNPs were identified and used to conduct the first genome-wide estimates of “SNP heritability” 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 the genetic component for resting behavior was negligible (indoors versus outside: permuted P = 0.465). A principal component analysis (PCA) segregated individuals into three groups which are characterized by 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 preference. Using a novel inversion genotyping assay developed to test for an association between inversion state and host choice, we detected a significant enrichment of the standard (non-inverted) 3Ra arrangement among cattle-fed mosquitoes (N=129) compared to human-fed (N=134; χ2, p=0.046) and versus all noncattle-fed individuals (N=234; χ2, 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 zoophily) in some populations so countermeasures can be implemented. A better understanding of the genetic basis for host preference in An. arabiensis may also improve vector control if cattle-biting mosquitoes can be genetically engineered and driven in a population, having an effect similar in concept to zooprophylaxis.Author Summary Increased insecticide treated bed net usage is associated with a shift in relative abundance from the highly anthropophilic and indoor-seeking vector species Anopheles gambiae s.s. to the more generalist species, Anopheles arabiensis. A genetic basis for these important phenotypes has not been determined, but recent work has linked variation in an odorant receptor to host-preference in another mosquito genus, Aedes aegypti. To begin addressing the genetic basis of these phenotypes, we performed a large-scale bloodmeal analysis at multiple villages in the Kilombero Valley, Tanzania.To limit the identification of genetic variation associated with different geographic locations, we focused our genetic analysis on the village of Lupiro. We sequenced a total of 48 genomes, including females that had fed on either human or cattle and that were resting indoors or outdoors. Our genomic analysis and subsequent follow-up with a novel molecular karyotyping assay revealed a relationship between individuals with the standard arrangement of the 3Ra inversion and preference for cattle. This is evidence supporting a substantial genetic basis for host preference in An. arabiensis. Further study is needed to examine allelic variation at candidate genes between the standard and inverted 3Ra. ER -