The Baltzegar Laboratory

Rapid evolution in an insect vector of disease

The mosquito, Ae. aegypti, is the major vector of dengue, chikungunya, zika, and yellow fever arboviruses. Each year dengue infects almost 400 million people annually, resulting in 96 million clinical cases. This mosquito disproportionately impacts the poorest members of society as they are the least able to protect themselves from disease exposure. While novel genetic engineering (RIDL and gene drive) and biological control (Wolbachia) methods are under development or in use on small scales, the primary means of controlling disease remains to reduce the adult population size through the use of chemical insecticides. We are examining the rapid evolution of knockdown resistance (kdr), a specific type of pyrethroid resistance characterized by mutations in the voltage-gated sodium channel gene (vgsc), in mosquitoes from Iquitos, Peru. We have found that in this population, kdr resistance evolved quickly and was defined by two periods of selection. The first was for a resistance allele containing one non-synonymous single nucleotide polymorphism (SNP) in the vgsc and the second was for a resistance allele containing two non-synonymous SNPs in the vgsc. The rapid increase of resistance alleles was aided by intense selection pressure and partial dominance of the resistance alleles. In on-going work, we are interrogating diplotypes in the vgsc that contain kdr resistance SNPs in an effort to understand how kdr resistance evolves in populations. This work will provide important insights on the mechanisms of resistance evolution in this disease vector.

Range expansion of a disease vector in a changing climate

Over the last 20 years, Ae. aegypti mosquitoes have undergone a range expansion in the Peruvian Amazon from the major city of Iquitos (population ~470,000) to smaller cities, towns, and villages in the region. This presents a public health problem as many of these communities are now at risk of arboviruses vectored by this species and public health agencies are not equipped to deal with additional outbreaks. With collaborators at University of California, Davis and Cornell University, we are examining the ecological and genomic impacts of this range expansion in the Peruvian Amazon region by comparing population genetic structure of communities that have newly established mosquito populations to those that have older populations. We are uncovering the invasion history of this species in the region and identifying source populations and time frames for establishment of new populations. We aim to gain insight into ecological factors and genetic traits governing population establishment in this species. Climate change models predict that the range expansion of Ae. aegypti into higher latitudes will accelerate over the next 50 years, therefore our results will be important in informing us how to best manage the impacts of a changing climate.

Urban evolution of insecticide resistance with complex socio-economic dimensions

 The mosquito Aedes albopictus, found abundantly in the southeastern USA, is a competent vector of West Nile Virus, Eastern Equine Encephalitis, dog heartworm, and dengue virus. As with Ae. aegypti, insecticides remain the most common and effective method of management for Ae. albopictus. However, insecticide resistance threatens the efficacy of chemical insecticides, thus limiting the viable tools vector management specialists have to use during disease outbreaks. With collaborators at North Carolina State University, we are examining the evolution of insecticide resistance in a population of Ae. albopictus from Wake County, North Carolina under a biological and socio-economic framework. We are using single nucleotide polymorphism (SNP, pronounced “snip”) genotyping combined with a custom-designed probe capture sequencing panel to identify novel pyrethroid resistance SNPs and reconstruct full haplotypes of the entire voltage-gated sodium channel. With this information, we will characterize all non-synonymous SNPs in the voltage-gated sodium channel that are present in the sequenced population, determine if there have been demographic changes in the Ae. albopictus population in response to the introduction of insecticide resistance haplotype frequencies, and incorporate these and other genetic data into a socio-economic model that will assess our hypothesis that socio-economic behaviors of Wake County residents contribute to increased frequency of insecticide resistance by correlating patterns of resistance haplotypes with social and economic factors. This study will allow us to gain insight into how human behaviors can directly impact management of insect vectors.

Evolutionary history and identification of the glucose-averse gene in the German cockroach, Blattella germanica

The German cockroach is the most widely distributed cockroach species in the world and is primarily found in human dwellings. It is a key transmitter of pathogenic microorganisms (e.g., E. coli) and is a major producer of allergens that cause asthma, especially in low-income children. In response to glucose-containing baits, the German cockroach has evolved glucose-aversion (GA) rapidly and multiple times (Florida, Russia, Puerto Rico) since 1989. Due to these rapid and multiple evolution events, we hypothesize that GA is an ancestral trait that still exists at low frequencies throughout the cockroach range. Phenotypic assays suggest that GA is governed by a single dominant gene, yet that gene has not been identified. Until recently, the large (~2Gb) and highly repetitive genome (55%) has been a barrier to successful identification of this gene, but with advances in genome sequencing techniques, we are able to answer this basic question. We are currently using quantitative trait loci (QTL) mapping to identify the causal gene of this unique behavior. The goal of this work is to better understand how an ancestral trait has been repurposed to increase survival in the face of modern pest management strategies and to improve control measures for this important insect species that negatively impacts low-income children.