THE GENETIC BASIS OF HOST PREFERENCE FOR CULEX PIPIENS ASSEMBLAGE MEMBERS, GLOBAL VECTORS OF MOSQUITO-BORNE DISEASE

Abstract

The transmission of vector-borne disease is a global public health concern. Not all mosquitoes are capable of transmitting disease agents. Among mosquitoes that can, host preference plays a major role in disease transmission dynamics. This is especially true for members of the Culex pipiens assemblage, where avian-and human-seeking behavior contributes to amplification of West Nile virus (WNv) in reservoir avian populations and its spillover into human populations. Host-seeking is mediated, in part, by chemosensory-related proteins that interact with and detect host odors and tastants. Encoded in the mosquito genome, these proteins include odorant-binding proteins (OBPs), odorant receptors (ORs), ionotropic receptors (IRs), and gustatory receptors (GRs). In this dissertation, I investigated both the divergent gene expression patterns and genomic variants that contribute to differences in mosquito host-seeking behavior. In Aim 1, I used homology-based annotation methods to manually curate the full set of IRs and GRs present in the reference genome for Culex quinquefasciatus, a globally distributed member of the Cx. pipiens assemblage. This revealed 216 IRs and 71 GRs, more than half of which were previously unidentified. In Aim 2, I analyzed gene expression at peak host-seeking time in female avian-seeking versus human-seeking Cx. pipiens antennae, the primary organ for olfaction in mosquitoes. This narrowed down a possible 524 candidate chemosensory genes to a shortlist of 17 IRs, 5 GRs, 30 ORs, and 13 OBPs which had the strongest patterns of differential expression among distinct bioforms within the Cx. pipiens assemblage. Thus, this list likely includes genes involved in host preference. In Aim 3, I analyzed the offspring of crosses between avian-seeking and human-seeking parental populations of Cx. pipiens, identifying a major effect quantitative trait locus (QTL) on chromosome 3. Additional multivariate analyses identified minor effect loci across all three chromosomes, pointing to a subset of nearby chemosensory genes that were also strongly differentially expressed in the antennae in Aim 2. It also suggested a possible role for early developmental differences in neurogenesis in determining host preference. Altogether, this research has generated several testable hypotheses to guide future functional work, and it begins to tease apart the genetic underpinnings of Cx. pipiens host-seeking behavior, a critical driver of WNv transmission in North America.