Patterns of Variation in an Olfactory Receptor of the Aedes aegypti Mosquito Contributing to a Preference for Human Odor

Abstract

The Aedes aegypti mosquito is found all over the world and acts as the primary vector for a number of infectious diseases, including dengue, Yellow Fever, Chikungunya, and Zika virus. Aedes aegypti traditionally is separated into two subspecies: Aedes aegypti formosus, the ancestral form, and Aedes aegypti aegypti, the derived form. The latter is known as the domestic subspecies because it shows a distinct preference for breeding in human homes and feeding on humans over animals. Recent research has found an olfactory receptor in Aedes aegypti that is implicated in this preference of A. a. aegypti. Or4 was found to have seven major alleles that varied in their sensitivities to sulcatone, a common component of human scent. Those alleles that were not sensitive were found more frequently in a population of A. a. formosus mosquitoes, while those that were sensitive to sulcatone were found more frequently in a population of A. a. aegypti. The aim of this thesis is to further explore the patterns of variation at the Or4 gene by sampling mosquitoes from Kenya, Uganda, and Senegal and analyzing the distribution of alleles as well as the mutations in the protein sequence to find functional variation. Findings support geography as a major determinant of the distribution of haplotypes at this locus. Findings also include what is beginning to look like an unprecedented amount of diversity in this gene. Although protein sequences were analyzed for possible signs of functional variation, individual amino acid changes need to be explored in more depth before anything definitive can be said. However, it looks like changes in sulcatone sensitivity and Or4 response may be related to both ligand-binding ability of the protein and the ability of the protein to bind to ORCO, the obligatory olfactory receptor co-receptor depending on the allele. The more this diversity and the function of this protein is understood, the better vector control strategies we will be able to implement to control outbreaks of infectious disease.