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The majority of mosquito-borne illness is spread by a few mosquito species that have evolved to specialize in biting humans, yet the precise causes of this behavioral shift are poorly understood. We address this gap in the arboviral vector Aedes aegypti. We first collect and characterize the behavior of mosquitoes from 27 sites scattered across the species' ancestral range in sub-Saharan Africa, revealing previously unrecognized variation in preference for human versus animal odor. We then use modeling to show that over 80% of this variation can be predicted by two ecological factors—dry season intensity and human population density. Finally, we integrate this information with whole-genome sequence data from 375 individual mosquitoes to identify a single underlying ancestry component linked to human preference. Genetic changes associated with human specialist ancestry were concentrated in a few …