Malaria caused an estimated 627, 000 deaths, mostly among African children in 2012. Anopheles gambiae is one of the most efficient vectors of malaria in the world. An. gambiae is highly anthropophilic, preferring the human host as a source of blood. An. gambiae enjoys an exceptional long life span, allowing a high probability to transmit malaria. An. gambiae exiles in adapting to diverse ecological environments, with a widespread geographical distribution from humid tropical rain forest to arid savanna across almost the whole Africa. An. gambiae practices its ritual of feeding on blood with a flavour of plasticity, with evidences of both indoor and outdoor biting, and resting behaviour, which asks for a diversity of vector control measures.;The stunning ability of An. gambiae to adapt to diverse ecological environments and the rich polymorphism of feeding related behaviour is considered to be related to the extensive chromosomal inversion polymorphism in the nature. Frequencies of inversions have been associated with multiple climate factors including aridity along transects starting from rain forests in southern Nigeria and Cameroon to arid savannas in the north. Frequencies of inversions vary inside and outside African huts, leading to differential human-vector contact rates. Frequencies of inversions run up and down while seasons come and go. However, ecological physiology and genetics of inversions in An. gambiae was not well explored, in contrast to numerous population studies of correlation of inversion frequency with ecological and environmental factors. A typical inversion contains hundreds of genes in strong linkage equilibrium, which makes mapping genes inside an inversion with any trait much less enjoyable process comparing to regular association or QTL mapping exercises.;To understand the genetic basis of "adaptation by inversion", we decided to take novel and powerful genomics approaches. First, by taking advantage of generations after generations of limited but ongoing gene flux between alternative gene arrangements in natural populations, we resequenced the genomes of female An. gambiae along a latitudinal cline in Cameroon. We were able to identify genetic regions highly differentiated between alternative gene arrangements. The genes or genetic factors involved in adaptation would have a higher probability located in those highly differentiated regions. Second, we systematically measured a set of ecological and epidemiological traits and found significant impacts of inverions on most of life history traits. In addition, we studied in uences of inversions on genome wide gene expression patterns by microarray. The effects of inversions on transcriptome were apparent, as transcript abundance of 10% to 40% genes were altered by inversions. We also identified genes with significant association with traits at the expression level. By combining results from the two different but complementary approaches, we were able to show that inversions have complex effects on multiple important traits, involving multiple genes/genetic factors, depending on sex and environments. The results also suggested a common mechanism of inversions' impact on phenotypes, probably by reprogramming energy metabolism and translation process through insulin/TOR pathway.
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