Julia E. Brown

Worldwide patterns of genetic differentiation imply multiple ‘domestications’ of Aedes aegypti, a major vector of human diseases

Understanding the processes by which species colonize and adapt to human habitats is particularly important in the case of disease-vectoring arthropods. The mosquito species Aedes aegypti, a major vector of dengue and yellow fever viruses, probably originated as a wild, zoophilic species in sub-Saharan Africa, where some populations still breed in tree holes in forested habitats. Many populations of the species, however, have evolved to thrive in human habitats and to bite humans. This includes some populations within Africa as well as almost all those outside Africa. It is not clear whether all domestic populations are genetically related and represent a single ‘domestication’ event, or whether association with human habitats has developed multiple times independently within the species. To test the hypotheses above, we screened 24 worldwide population samples of Ae. aegypti at 12 polymorphic microsatellite loci. We identified two distinct genetic clusters: one included all domestic populations outside of Africa and the other included both domestic and forest populations within Africa. This suggests that human association in Africa occurred independently from that in domestic populations across the rest of the world. Additionally, measures of genetic diversity support Ae. aegypti in Africa as the ancestral form of the species. Individuals from domestic populations outside Africa can reliably be assigned back to their population of origin, which will help determine the origins of new introductions of Ae. aegypti.

HUMAN IMPACTS HAVE SHAPED HISTORICAL AND RECENT EVOLUTION IN AEDES AEGYPTI, THE DENGUE AND YELLOW FEVER MOSQUITO

Although anthropogenic impacts are often considered harmful to species, human modifications to the landscape can actually create novel niches to which other species can adapt. These “domestication” processes are especially important in the context of arthropod disease vectors, where ecological overlap of vector and human populations may lead to epidemics. Here, we present results of a global genetic study of one such species, the dengue and yellow fever mosquito, Aedes aegypti, whose evolutionary history and current distribution have been profoundly shaped by humans. We used DNA sequences of four nuclear genes and 1504 single nucleotide polymorphism (SNP) markers developed with restriction‐site associated DNA (RAD) sequencing to test the hypothesis that Ae. aegypti originated in Africa, where a domestic form arose and spread throughout the tropical and subtropical world with human trade and movement. Results confirmed African ancestry of the species, and supported a single subspeciation event leading to the pantropical domestic form. In addition, genetic data strongly supported the hypothesis that human trade routes first moved domestic Ae. aegypti out of Africa into the New World, followed by a later invasion from the New World into Southeast Asia and the Pacific. These patterns of domestication and invasion are relevant to many species worldwide, as anthropogenic forces increasingly impact evolutionary processes.

Urban population genetics of slum‐dwelling rats (Rattus norvegicus) in Salvador, Brazil

Throughout the developing world, urban centres with sprawling slum settlements are rapidly expanding and invading previously forested ecosystems. Slum communities are characterized by untended refuse, open sewers and overgrown vegetation, which promote rodent infestation. Norway rats (Rattus norvegicus) are reservoirs for epidemic transmission of many zoonotic pathogens of public health importance. Understanding the population ecology of R. norvegicus is essential to formulate effective rodent control strategies, as this knowledge aids estimation of the temporal stability and spatial connectivity of populations. We screened for genetic variation, characterized the population genetic structure and evaluated the extent and patterns of gene flow in the urban landscape using 17 microsatellite loci in 146 rats from nine sites in the city of Salvador, Brazil. These sites were divided between three neighbourhoods within the city spaced an average of 2.7 km apart. Surprisingly, we detected very little relatedness among animals trapped at the same site and found high levels of genetic diversity, as well as structuring across small geographical distances. Most FST comparisons among sites were statistically significant, including sites <400 m apart. Bayesian analyses grouped the samples in three genetic clusters, each associated with distinct sampling sites from different neighbourhoods or valleys within neighbourhoods. These data indicate the existence of complex genetic structure in R. norvegicus in Salvador, linked to the heterogeneous urban landscape. Future rodent control measures need to take into account the spatial and temporal linkage of rat populations in Salvador, as revealed by genetic data, to develop informed eradication strategies.

Origin of the dengue fever mosquito, Aedes aegypti, in California.

Dengue fever is among the most widespread vector-borne infectious diseases. The primary vector of dengue is the Aedes aegypti mosquito. Ae. aegypti is prevalent in the tropics and sub-tropics and is closely associated with human habitats outside its native range of Africa. While long established in the southeastern United States of America where dengue is re-emerging, breeding populations have never been reported from California until the summer of 2013. Using 12 highly variable microsatellite loci and a database of reference populations, we have determined that the likely source of the California introduction is the southeastern United States, ruling out introductions from abroad, from the geographically closer Arizona or northern Mexico populations, or an accidental release from a research laboratory. The power to identify the origin of new introductions of invasive vectors of human disease relies heavily on the availability of a panel of reference populations. Our work demonstrates the importance of generating extensive reference databases of genetically fingerprinted human-disease vector populations to aid public health efforts to prevent the introduction and spread of vector-borne diseases.

Aedes aegypti Mosquitoes Imported into the Netherlands, 2010

During summer 2010, Aedes aegypti mosquitoes were discovered in the Netherlands. Using genetic markers, we tracked the origin of these mosquitoes to a tire shipment from Miami, Florida, USA. Surveillance of tire exports from the United States should be included as part of a comprehensive surveillance system.

Genetic Diversity of Brazilian Aedes aegypti: Patterns following an Eradication Program

Background Aedes aegypti is the most important vector of dengue fever in Brazil, where severe epidemics have recently taken place. Ae. aegypti in Brazil was the subject of an intense eradication program in the 1940s and 50s to control yellow fever. Brazil was the largest country declared free of this mosquito by the Pan-American Health Organization in 1958. Soon after relaxation of this program, Ae. aegypti reappeared in this country, and by the early 1980s dengue fever had been reported. The aim of this study is to analyze the present-day genetic patterns of Ae. aegypti populations in Brazil. Methodology/Principal Findings We studied the genetic variation in samples of 11 widely spread populations of Ae. aegypti in Brazil based on 12 well-established microsatellite loci. Our principal finding is that present-day Brazilian Ae. aegypti populations form two distinct groups, one in the northwest and one in the southeast of the country. These two groups have genetic affinities to northern South American countries and the Caribbean, respectively. This is consistent with what has been reported for other genetic markers such as mitochondrial DNA and allele frequencies at the insecticide resistance gene, kdr. Conclusions/Significance We conclude that the genetic patterns in present day populations of Ae. aegypti in Brazil are more consistent with a complete eradication of the species in the recent past followed by re-colonization, rather than the alternative possibility of expansion from residual pockets of refugia. At least two colonizations are likely to have taken place, one from northern South American countries (e.g., Venezuela) that founded the northwestern group, and one from the Caribbean that founded the southeastern group. The proposed source areas were never declared free of Ae. aegypti.

Closely-related Borrelia burgdorferi (sensu stricto) strains exhibit similar fitness in single infections and asymmetric competition in multiple infections

BackgroundWild hosts are commonly co-infected with complex, genetically diverse, pathogen communities. Competition is expected between genetically or ecologically similar pathogen strains which may influence patterns of coexistence. However, there is little data on how specific strains of these diverse pathogen species interact within the host and how this impacts pathogen persistence in nature. Ticks are the most common disease vector in temperate regions with Borrelia burgdorferi, the causative agent of Lyme disease, being the most common vector-borne pathogen in North America. Borrelia burgdorferi is a pathogen of high public health concern and there is significant variation in infection phenotype between strains, which influences predictions of pathogen dynamics and spread.MethodsIn a laboratory experiment, we investigated whether two closely-related strains of B. burgdorferi (sensu stricto) showed similar transmission phenotypes, how the transmission of these strains changed when a host was infected with one strain, re-infected with the same strain, or co-infected with two strains. Ixodes scapularis, the black-legged tick, nymphs were used to sequentially infect laboratory-bred Peromyscus leucopus, white-footed mice, with one strain only, homologous infection with the same stain, or heterologous infection with both strains. We used the results of this laboratory experiment to simulate long-term persistence and maintenance of each strain in a simple simulation model.ResultsStrain LG734 was more competitive than BL206, showing no difference in transmission between the heterologous infection groups and single-infection controls, while strain BL206 transmission was significantly reduced when strain LG734 infected first. The results of the model show that this asymmetry in competition could lead to extinction of strain BL206 unless there was a tick-to-host transmission advantage to this less competitive strain.ConclusionsThis asymmetric competitive interaction suggests that strain identity and the biotic context of co-infection is important to predict strain dynamics and persistence.

Phylogeography and Spatio-Temporal Genetic Variation of Aedes aegypti (Diptera: Culicidae) Populations in the Florida Keys

ABSTRACT Aedes aegypti (L.) is the principal mosquito vector of dengue fever, the second-most deadly vector-borne disease in the world. In Ae. aegypti and other arthropod disease vectors, genetic markers can be used to inform us about processes relevant to disease spread, such as movement of the vectors across space and the temporal stability of vector populations. In late 2009, 27 locally acquired cases of dengue fever were reported in Key West, FL. The last dengue outbreak in the region occurred in 1934. In this study, we used 12 microsatellite loci to examine the genetic structure of 10 Ae. aegypti populations from throughout the Florida Keys and Miami to assess gene flow along the regions main roadway, the Overseas Highway. We also assessed temporal genetic stability of populations in Key West to determine whether the recent outbreak could have been the result of a new introduction of mosquitoes. Though a small amount of geographic genetic structure was detected, our results showed high overall genetic similarity among Ae. aegypti populations sampled in southeastern Florida. No temporal genetic signal was detected in Key West populations collected before and after the outbreak. Consequently, there is potential for dengue transmission across southeastern Florida; renewed mosquito control and surveillance measures should be taken.

Genetics and Morphology of Aedes aegypti (Diptera: Culicidae) in Septic Tanks in Puerto Rico

ABSTRACT Dengue viruses, primarily transmitted by the mosquito Aedes aegypti (L.), affect an estimated 50–100 million people yearly. Traditional approaches to control mosquito population numbers, such as the use of pesticides, have had only limited success. Atypical mosquito behavior may be one reason why current vector control efforts have been less efficacious than expected. In Puerto Rico, for example, adult Ae. aegypti have been observed emerging from septic tanks. Interestingly, adults emerging from septic tanks are larger on average than adults collected from surface containers. To determine whether adults colonizing septic tanks constitute a separate Ae. aegypti population, we used 12 previously validated microsatellite loci to examine adult mosquitoes collected from both septic tanks and surface containers, but found no evidence to suggest genetic differentiation. Size differences between septic tank and surface mosquitoes were reduced when nutrient levels were held constant across experimental groups. Despite the absence of evidence suggesting a genetic difference between experimental groups in this study, Ae. aegypti emerging from septic tanks may still represent a more dangerous phenotype and should be given special consideration when developing vector control programs and designing public health interventions in the future.

Microhabitat Partitioning of Aedes simpsoni (Diptera: Culicidae)

ABSTRACT Yellow fever virus is a reemerging infection responsible for widespread, sporadic outbreaks across Africa. Although Aedes aegypti (L.) is the most important vector globally, in East Africa, epidemics may be vectored by Aedes bromeliae (Theobald), a member of the Aedes simpsoni (Theobald) species complex. The Ae. simpsoni complex contains 10 subspecies, of which Ae. bromeliae alone has been incriminated as a vector of yellow fever virus. However, morphological markers cannot distinguish Ae. bromeliae from conspecifics, including the sympatric and non-anthropophilic Aedes lilii (Theobald). Here, we used three sequenced nuclear markers to examine the population structure of Ae. simpsoni complex mosquitoes collected from diverse habitats in Rabai, Kenya. Gene trees consistently show strong support for the existence of two clades in Rabai, with segregation by habitat. Domestic mosquitoes segregate separately from forest-collected mosquitoes, providing evidence of habitat partitioning on a small spatial scale (<5 km). Although speculative, these likely represent what have been described as Ae. bromeliae and Ae. lilii, respectively. The observation of high levels of diversity within Rabai indicates that this species complex may exhibit significant genetic differentiation across East Africa. The genetic structure, ecology, and range of this important disease vector are surprisingly understudied and need to be further characterized.