A number of statistical techniques have been developed to test for the occurrence of recombination within a given gene region and to determine the bounds of the recombinational event. Unfortunately, we know very little about the relative strengths and weaknesses of these techniques. We propose to evaluate the performance of different methods to detect recombination from a set of aligned DNA sequences. The statistical evaluation of these methods will provide valuable information to select a method for detecting recombination. Moreover, the identification of the conditions under which different methods are more likely to be misleading will provide more robust conclusions about the occurrence of recombination. By understanding which factors are most relevant in the detection of recombination, we will be able to develop better methods and to improve existing techniques. Finally, the best performing techniques will be used to scan the HIV database for the presence of recombination and for the reevaluation of circulating recombinant forms (CRF). Understanding the generation of genetic diversity of HIV-1 is key to fighting its ability to evolve solutions to drug therapies and vaccine attempts. Recombination and mutation are the creative forces for genetic diversity. Studies in HIV-1 have shown recombination to have a significant impact on our understanding of the history of gene genealogies and arguments based on these phylogenies, including estimates of genetic diversity. Our study will provide researchers with an assessment of the available statistical tools for detecting recombination and guidelines as to when each tool works best. It will also provide the first comprehensive assessment of the impact of recombination in shaping the current genetic diversity of HIV-1 using statistically validated techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM066276-01
Application #
6508638
Study Section
Genetics Study Section (GEN)
Program Officer
Eckstrand, Irene A
Project Start
2002-07-01
Project End
2006-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$137,970
Indirect Cost
Name
Brigham Young University
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
City
Provo
State
UT
Country
United States
Zip Code
84602
Castro-Nallar, Eduardo; PĂ©rez-Losada, Marcos; Burton, Gregory F et al. (2012) The evolution of HIV: inferences using phylogenetics. Mol Phylogenet Evol 62:777-92
Castro-Nallar, Eduardo; Cortez-San Martin, Marcelo; Mascayano, Carolina et al. (2011) Molecular phylodynamics and protein modeling of infectious salmon anemia virus (ISAV). BMC Evol Biol 11:349
Tazi, Loubna; Imamichi, Hiromi; Hirschfeld, Steven et al. (2011) HIV-1 infected monozygotic twins: a tale of two outcomes. BMC Evol Biol 11:62
Woolley, Steven M; Posada, David; Crandall, Keith A (2008) A comparison of phylogenetic network methods using computer simulation. PLoS One 3:e1913
Keele, Brandon F; Tazi, Loubna; Gartner, Suzanne et al. (2008) Characterization of the follicular dendritic cell reservoir of human immunodeficiency virus type 1. J Virol 82:5548-61
Carvajal-Rodriguez, Antonio; Posada, David; Perez-Losada, Marcos et al. (2008) Disease progression and evolution of the HIV-1 env gene in 24 infected infants. Infect Genet Evol 8:110-20
Nickle, David C; Heath, Laura; Jensen, Mark A et al. (2007) HIV-specific probabilistic models of protein evolution. PLoS One 2:e503
Carvajal-Rodriguez, Antonio; Crandall, Keith A; Posada, David (2007) Recombination favors the evolution of drug resistance in HIV-1 during antiretroviral therapy. Infect Genet Evol 7:476-83
Szklarczyk, Radek; Heringa, Jaap; Pond, Sergei Kosakovsky et al. (2007) Rapid asymmetric evolution of a dual-coding tumor suppressor INK4a/ARF locus contradicts its function. Proc Natl Acad Sci U S A 104:12807-12
Bello, Gonzalo; Casado, Concepcion; Garcia, Soledad et al. (2007) Lack of temporal structure in the short term HIV-1 evolution within asymptomatic naive patients. Virology 362:294-303

Showing the most recent 10 out of 23 publications