It is children living in Africa south of the Sahara that bear the brunt of morbidity and mortality caused by Plasmodium falciparum. Here, traditional methods of vector control have been least effective, and the mitigating role of permethrin-impregnated bednets is threatened by emergence of permethrin resistance in the primary vector, Anopheles gambiae. Effective strategies for monitoring and managing the spread of insecticide resistance will depend upon detailed information about the genetic structure of vector populations. This same information is essential for future genetic control strategies aimed at the replacement of vector by nonvector populations. In this context, it is important to address the hypothesis that different chromosomal forms of An. gambiae are reproductively isolated, using independent molecular markers. It is also a premise of this proposal that the requisite information extends beyond An. gambiae to a second vector of major importance, its sibling species An. arabiensis. The possibility that An. gambiae may be hybridizing productively with An. arabiensis suggests that undesirable traits such as insecticide resistance could be exchanged between species. Past efforts to conclusively demonstrate gene flow between these vectors ahve been complicated by the confounding explanation of recent common ancestry and the contadictory evidence concerning their status as sister taxa within the species complex known as the An. gambia complex. The Y chromosome provides a powerful tool to attack questions at the population level and above, not only because it is nonrecombining and paternally transmitted, but also because it cannot cross barriers since male hybrids are sterile. The main goal of this proposal is the development and application of DNA sequence markers on the Y chromosome (microsatellites, insertion-deletions, and base substitutions) that, in combination with other markers, will help solve three interrelated questions: (1) Are An. gambiae and An. arabiensis sister taxa? (2) How much gene flow is occurring between them, and which genomic regions are susceptible? (3) How much gene flow is occurring between chromosomal forms of An. gambiae?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI044003-05
Application #
6624530
Study Section
Special Emphasis Panel (ZRG5-TMP (01))
Program Officer
Aultman, Kathryn S
Project Start
1998-12-01
Project End
2004-11-30
Budget Start
2002-12-01
Budget End
2004-11-30
Support Year
5
Fiscal Year
2003
Total Cost
$220,866
Indirect Cost
Name
University of Notre Dame
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
824910376
City
Notre Dame
State
IN
Country
United States
Zip Code
46556
Krzywinski, Jaroslaw; Chrystal, Mathew A; Besansky, Nora J (2006) Gene finding on the Y: fruitful strategy in Drosophila does not deliver in Anopheles. Genetica 126:369-75
Sharakhov, Igor V; White, Bradley J; Sharakhova, Maria V et al. (2006) Breakpoint structure reveals the unique origin of an interspecific chromosomal inversion (2La) in the Anopheles gambiae complex. Proc Natl Acad Sci U S A 103:6258-62
Stump, Aram D; Shoener, Jennifer A; Costantini, Carlo et al. (2005) Sex-linked differentiation between incipient species of Anopheles gambiae. Genetics 169:1509-19
Krzywinski, Jaroslaw; Sangare, Djibril; Besansky, Nora J (2005) Satellite DNA from the Y chromosome of the malaria vector Anopheles gambiae. Genetics 169:185-96
Barnes, M J; Lobo, N F; Coulibaly, M B et al. (2005) SINE insertion polymorphism on the X chromosome differentiates Anopheles gambiae molecular forms. Insect Mol Biol 14:353-63
Stump, Aram D; Fitzpatrick, Meagan C; Lobo, Neil F et al. (2005) Centromere-proximal differentiation and speciation in Anopheles gambiae. Proc Natl Acad Sci U S A 102:15930-5
Stump, Aram D; Atieli, Francis K; Vulule, John M et al. (2004) Dynamics of the pyrethroid knockdown resistance allele in western Kenyan populations of Anopheles gambiae in response to insecticide-treated bed net trials. Am J Trop Med Hyg 70:591-6
Krzywinski, Jaroslaw; Nusskern, Deborah R; Kern, Marcia K et al. (2004) Isolation and characterization of Y chromosome sequences from the African malaria mosquito Anopheles gambiae. Genetics 166:1291-302
Krzywinski, Jaroslaw; Besansky, Nora J (2003) Molecular systematics of Anopheles: from subgenera to subpopulations. Annu Rev Entomol 48:111-39
Besansky, N J; Krzywinski, J; Lehmann, T et al. (2003) Semipermeable species boundaries between Anopheles gambiae and Anopheles arabiensis: evidence from multilocus DNA sequence variation. Proc Natl Acad Sci U S A 100:10818-23

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