Systems genetic analysis of inversion polymorphisms in the malaria mosquito Anopheles gambiae

Abstract

Inversion polymorphisms in the African malaria vector segregate along climatic gradients of aridity. Despite indirect evidence of their adaptive significance, little is known of the phenotypic targets of selection or the underlying genetic mechanisms. Here we adopt a systems genetics approach to explore the interaction of two inversions on opposite arms of chromosome 2 with gender, climatic conditions, and one another. We measure organismal traits and transcriptional profiles in 8-d-old adults of both sexes and four alternative homokaryotypic classes reared under two alternative climatic regimes. We show that karyotype strongly influences both organismal traits and transcriptional profiles but that the strength and direction of the effects depend upon complex interactions with gender and environmental conditions and between inversions on independent arms. Our data support the suppressed recombination model for the role of inversions in local adaptation, and-supported by transcriptional and physiological measurements following perturbation with the drug rapamycin-suggest that one mechanism underlying their adaptive role may be the maintenance of energy homeostasis.

Association mapping desiccation resistance within chromosomal inversions in the African malaria vectorAnopheles gambiae

“…Of these 44 genes, 35 showed significant differences in expression between arrangements of In(2La). This fraction of differentially expressed genes with significant SNPs, 79.5% (35/44), is much higher than the overall fraction of differentially expressed genes within In(2La) between arrangements (~60%; Cheng et al 2018). Two of our top-ranking candidate genes have presumed roles in response to environmental stimulus.…”

“…Most significant SNPs were found in non-coding regions: we found only four synonymous variants among our set of significant sites, and no nonsynonymous variants. Previous studies have found many differences in transcription between inversion arrangements at In(2La) (Cassone et al 2011;Cheng et al 2018), allowing us to ask whether the same genes containing significant SNPs also showed evidence for differential expression. We crossreferenced expression profiles from Cheng et al (2018) with our list of 57 candidate genes and found data for 44 of them.…”

“…This hypothesis has been supported by physiological testing in laboratory colonies (Fouet et al 2012;Gray et al 2009;Rocca et al 2009). However, despite transcriptional profiling in the laboratory (Cassone et al 2011;Cheng et al 2018) and genome resequencing along a cline (Cheng et al 2012), the mechanistic basis of this presumably adaptive advantage remains elusive.…”

Assessing connectivity despite high diversity in island populations of a malaria mosquito

“…It has been recently implicated in nutritional homeostasis in Drosophila [54] and is known to interact with the TOR pathway [55], which has been identified as a target of ecological adaptation in Drosophila [56, 57] and An. gambiae [58]. The sweep appears largely confined to island individuals in the LVB, but the cluster of haplotypes also includes those from Gabon, Burkina Faso, and Kenya.…”

Fine-mapping complex inversion breakpoints and investigating somatic pairing in theAnopheles gambiaespecies complex using proximity-ligation sequencing

“…Drosophila species has found chromosomal inversion structure to have little effect on gene expression patterns (Huang et al 2015;Fuller et al 2016;Lavington and Kern 2017;Said et al 2018;Cheng et al 2018) . Our observation that somatic pairing is disrupted only partially and only in the relatively small regions immediately surrounding inversion breakpoints is consistent with these observations and suggests that dipteran chromatin structures are particularly resilient to changes imposed by genome structure polymorphism.…”