Sand flies infect more than one million people annually with Leishmania
parasites and other bacterial and viral pathogens. Progress in
understanding sand fly adaptations to xenobiotics, such as insecticides
has been hampered by the limited availability of genomic resources. Here
we sequenced, assembled and annotated the transcriptomes of 11
phlebotomine sand fly species, and used them to generate new
evolutionary insights pertaining to their adaptations to xenobiotics,
including those contributing to insecticide resistance. We annotated and
performed large-scale phylogenetic comparisons of more than 2,700 sand
fly genes from the five major detoxification enzyme families, Cytochrome
P450s (CYPs), Glutathione-S-Transferases (GSTs),
UDP-Glycosyltransferases (UGTs), Carboxyl/Cholinesterases (CCEs) and
ATP-Binding Cassette (ABC) Transporters. This comparative approach
uncovered that sand flies have evolved diverse CYP and GST repertoires,
with striking expansions in gene groups encoding for potential
xenobiotic metabolizers. Furthermore, we identified conserved orthologs
for two primary insecticide targets, acetylcholinesterase-1 (Ace1) and
Voltage Gated Sodium Channel (VGSC). This work provides novel biological
insights and valuable genomic resources for enabling sand fly research
in xenobiotic adaptation and insecticide resistance.