Manual curation of chemosensory genes and antennal RNAseq reveals candidate genes associated with host preference in Culex pipiens assemblage members

Mosquito host preference plays an important role in vector-borne disease transmission, dependent on host-specific volatile detection by a finely tuned chemosensory system. Here, we manually curated two highly divergent chemosensory gene families – ionotropic receptors (IRs) and gustatory receptors (GRs) – for the first time in a chromosome-level genome assembly for Culex quinquefasciatus . We annotated 216 IRs and 71 GRs, over half of which were previously unidentified. Consistent with other Culicinae mosquitoes, IRs showed strong expansion, pseudogenization, and high sequence divergence. These new annotations were applied to investigate differences in antennal expression between avian- and mammal-preferring Cx. pipiens assemblage members, narrowing a list of over 500 candidate chemosensory genes to 17 IRs, 5 GRs, 30 ORs, and 13 OBPs strongly associated with host preference. These results open direct avenues to further investigate the genetic basis for human- and avian-seeking behavior in Cx. pipiens , which influences arboviral transmission dynamics around the globe. • Manual curation of IRs and GRs in the chromosome-level Cx. quinquefasciatus JHB2020 genome assembly reveals 216 IRs and 71 GRs, more than half of which were previously unidentified by RefSeq annotation. • Phylogenetic analysis supports large expansion of IR gene family observed in Cx. quinquefasciatus relative to other mosquito species. • Comparative differential expression analysis of the antennal transcriptome in avian-seeking Cx. pipiens form pipiens and human-seeking form molestus reveals shortlist of IRs, GRs, ORs, and OBPs associated with host preference.