A major 6 Mb superlocus is involved in pyrethroid resistance in the common bed bugCimex lectularius

Abstract

In the last few years, the bed bug Cimex lectularius has been an increasing problem worldwide, mainly due to the development of insecticide resistance to pyrethroids. The characterization of resistance alleles is a prerequisite to improve surveillance and resistance management. To identify genomic variants associated with pyrethroid resistance in Cimex lectularius, we compared the genetic composition of two recent and resistant populations with that of two ancient-susceptible strains using a genome-wide pool-seq design. We identified a large 6 Mb "superlocus" showing particularly high genetic differentiation and association with the resistance phenotype. This superlocus contained several clustered resistance genes, and was also characterized by a high density of structural variants (inversions, duplications). The possibility that this superlocus constitute a resistance "supergene" that evolved after the clustering of alleles adapted to insecticide and after reduction in recombination is discussed.

Transcriptomic response to pyrethroid treatment in closely related bed bug strains varying in resistance

“…However, a few outlier SNPs were detected, including within genomic regions annotated as promoters, that might be involved in the constitutive expression difference observed. These SNPs were part of the most differentiated loci detected in the whole genome analysis we conducted previously (Haberkorn et al, 2023). Four of these mutations were detected in introns of an over-expressed cuticular gene (106666062).…”

“…Other categories were separated as: "Other detox" (64), "Cuticle" (113), "Insecticide target and nervous system" (31), and "Redox homeostasis" (14 genes). Details about those 431 genes are provided in Haberkorn et al 2023. Analysis of enrichment of candidate genes in each resistance category were performed by comparing their proportions in genomic regions of interest with whole genome, using R/stats default package (proportion test with FDR correction for multiple comparisons).…”

“…Outlier SNPs were obtained from our previous genomic analysis based on the intersection of three criterion : (i) the differentiation between the two strains originating from London should be high (top 5% F ST s), (ii) alleles should be in a derived state, if one considers that the alleles of the reference genome (the insecticide susceptible Harlan strain) are ancestral (at least for loci involved in insecticide resistance), (iii) (derived) alleles should be in higher frequency in London Field than in London Lab. With these criteria applied using only the two London strains, 100,941 outlier SNPs were detected (versus 576 in Haberkorn et al (2023) that included another set of strains). Among these SNPs, 59,537 were distributed in 4,987 genes (out of the 12,187).…”

“…Outliers SNPs were determined as having their F ST value in top 5% quantile (i.e. empirical pF ST < 0.05) and the frequency of alternative allele (F al t ) higher in London Field (LF) than London Lab (LL), according to our previous population genomic analysis Haberkorn et al (2023). The position of each SNP is given, together with the distance to the nearest gene (Dist.)…”

“…To provide insights into the genomic sequences underlying insecticide resistance, we recently contrasted allele frequencies between resistant and susceptible strains of C. lectularius through a DNA pool-sequencing approach (Haberkorn et al, 2023). A 6 Mb superlocus showing high genetic differentiation between resistant and susceptible strains was identified.…”