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Title: Ecological genomics and speciation in malaria vector mosquitoes
Author: Clarkson, Christopher
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2015
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Malaria vector control campaigns generate rapid changes to ecology with concomitant selective pressures on their targets. Malaria mosquitoes, therefore, present an excellent system for studying ecological adaptation alongside the medical importance of understanding the evolution of insecticide resistance. Adaptive introgression allows rapid adaptation through gene flow of fitness conferring loci from another species and, though commonly reported in plants, it is thought to be rare in animals. Using a whole genome sequencing approach, the impact of an insecticide resistance locus introgression between malaria vectors, A. gambiae and A. coluzzii, was investigated. The resistance locus lies within a genomic ‘island’, a large region of genome, highly divergent between the two species. Our results revealed that the inter-specific introgression transferred, not only the kdr resistance locus, but ~1.5% of the surrounding genome from A. gambiae into A. coluzzii, homogenising the entire island. These findings bring into debate hypotheses of the genomic islands’ role in the speciation of these mosquitoes, as no increase in hybridisation had been recorded despite the large introgressed region sweeping through the A. coluzzii population. From a control perspective, these results also demonstrate how quickly a species can react to anthropogenic pressure, to escape chemical control. In Ghana, as across much of A. gambiae and A. coluzzii’s sympatric range, low levels of hybridisation are recorded, a fact that was in part used to validate the recent elevation to specific status of the pair. However, in the far-west of their range, much higher levels of hybridisation are reported. A microsatellite study, sampling a transect across a region known for high gene-flow in Guinea Bissau, was carried out to investigate this phenomenon, discovering a hybridisation hot-spot in the coastal region. We augmented this microsatellite study with WGS data, sequencing individuals from coastal and inland sites. Results revealed that in the coastal region alongside molecularly genotyped hybrids, mosquitoes which had been genotyped as pure species appeared to be admixed. Ancestry informative markers demonstrated asymmetric introgression from A. coluzzii into the coastal A. gambiae and, with A. coluzzii numbers falling in the region, species collapse or perhaps hybrid speciation may be occurring. In these high gene flow regions the mosquitoes do not conform to distinct taxonomic units and we show that whole genome characterisation is necessary to understand the evolutionary dynamics. Understanding insecticide resistance is a major motivation in researching the genomics of malaria vectors, as resistance threatens the success of control campaigns. The voltage gated sodium channel (VGSC), is of particular interest, carrying several loci known to confer insecticide resistance in A. gambiae and A. coluzzii. We utilised 765 WGS individuals from the Anopheles gambiae 1000 Genomes Project, to investigate gene flow and evolution in this important gene. The data was phased then displayed in a network approach, to enable relationships between the VGSC haplotypes to be discerned. Striking was both the evidence for an abundance of long range gene flow, with resistant haplotypes shared across vast geographical distances, and for the high numbers and placement of non-synonymous mutations on haplotypes carrying resistance mutations. A hitherto unknown complexity of both the spread of resistance and protein altering mutations was found, suggesting current molecular assays may need revising. Insecticide resistance is perhaps less well understood in another major malaria vector, A. arabiensis. Recent advances in genomic resources for the species enabled us to carry out a genome wide association study (GWAS) to identify insecticide resistance candidates. To produce confidence in results, a pool-seq approach was taken, sequencing and comparing the allele frequencies of over 1000 resistance phenotyped individuals. Several candidate regions were found, the strongest of which we investigated further. The ~225kb region on the 2R chromosome arm straddled a cluster of cytochrome P450 genes, known to be involved in detoxification, including CYP6P2, a gene previous linked to pyrethroid resistance in this species. These results revealed this technique to be both viable and useful for identifying phenotype/genotype candidates in wild populations of mosquitoes. The work herein demonstrates that the genomic study of Anopheles malaria vectors is not just powerful in medical context, but that these animals provide excellent natural systems for evolutionary study. A. gambiae in Ghana and in Guinea Bissau provide natural experiments contrasting how species integrity reacts in low and high gene flow situations, while investigations into the VGSC and insecticide resistance in A. arabiensis shine light on how organisms adapt to rapidly changing ecologies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Q Science (General)