Chromosomal Evolution of Malaria Vectors
Peery, Ashley Nicole
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International malaria control initiatives such as the Roll Back Malaria Initiative (RBM) and the Medicines for Malaria Venture (MMV) mobilize resources and spur research aimed at vector control as well as the treatment and eventual eradication of the disease. These efforts have managed to reduce incidence of malaria by an estimated 37% worldwide since 2000. However, despite the promising success of control efforts such as these, the World Health Organization reports a staggering 438,000 deaths from malaria in 2015. The continuing high death toll of malaria as well as emerging insecticide and antimalarial drug resistance suggests that while encouraging, success in reducing malaria incidence may be tenuous. Current vector control strategies are often complicated by ecological and behavioral heterogeneity of vector mosquito populations. As an additional obstruction, mosquito genomes are highly plastic as evidenced by the wealth or chromosomal inversions that have occurred in this genus. Chromosomal inversions have been correlated with differences in adaptation to aridity, insecticide resistance, and differences in resting behavior. However, a good understanding of the molecular mechanisms for inversion generation is still lacking. One possible contributor to inversion formation in Anopheles mosquitoes includes repetitive DNA such as transposable elements (TEs), tandem repeats (TRs) and inverted repeats (IRs). This dissertation provides physical maps for two important malaria vectors, An. stephensi and An. albimanus (Ch.2 and Ch. 3) and then applies those maps to the identification of inversion breakpoints in malaria mosquitoes. Repeat content of each chromosomal arm and the molecular characterization of lineage specific breakpoints is also investigated (Ch. 2 and Ch.4). Our study reveals differences in patterns of chromosomal evolution of Anopheles mosquitoes vs. Drosophila. First, mosquito chromosomes tend to shuffle as intact elements via whole arm translocations and do not under fissions or fusions as seen in fruitflies. Second, the mosquito sex chromosome is changing at a much higher rate relative to the autosomes in malaria mosquitoes than in fruit flies. Third, our molecular characterization of inversion breakpoints indicates that TEs and TRs may participate in inversion genesis in an arm specific manner.
General Audience Abstract
Malaria is a complex and devastating disease vectored by the bite of a female Anopheles mosquito. This disease claimed an estimated 438,000 lives in 2015. The mobilization of funding and resources as part of global malaria eradication initiatives have reduced the global incidence of malaria by 37% in the last 15 years. Deaths from malaria are also 60% lower vs. the year 2000. These promising gains are threatened by the ability of Anopheles mosquitoes to adapt in the face of malaria control efforts. Anopheles mosquito chromosomes are known to be highly plastic, as evidenced by numerous chromosomal inversions. Recent years have seen increases in insecticide resistance, and behavioral change in mosquito populations that allow them to avoid insecticides and remain prolific vectors of disease. This ability of mosquito vectors to adapt threatens to unravel recent progress towards a malaria free world. The projects presented in this dissertation explore mechanisms of chromosomal evolution, specifically the potential role of repetitive DNA in the generation of chromosomal inversions. The exploration of chromosomal inversions was facilitated by the creation of physical maps for Anopheles species. Prominent malaria vectors An. stephensi andAn. albimanus were physically mapped in Chapter 2 and Chapter 3 respectively. In chapter 1 and chapter 3 physical maps are utilized for the identification of chromosomal inversion breakpoints using 2 species (Ch. 2) and many species (Ch. 4). Repeat content was quantified along each chromosomal arm (Ch 2,4) and in inversion breakpoint regions (Ch 3). This dissertation presents physical maps for two important malaria species that have been applied to the study of chromosomal evolution and will also serve as community tools for further study of malaria mosquitoes. Our work on chromosomal evolution has revealed the Anopheles chromosomes tend to undergo translocations as intact elements and do not under fissions and fusions as seen in fruitflies. We also find that the malaria mosquito sex chromosome changes much more rapidly relative to the autosomes than in fruitflies. Additionally, repetitive DNA including transposable elements (TEs) and tandem repeats (TRs) may be encouraging chromosomal inversions but with differing roles on different chromosomal arms.
- Doctoral Dissertations