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Related Experiment Videos

Robust inference of positive selection from recombining coding sequences.

Konrad Scheffler1, Darren P Martin, Cathal Seoighe

  • 1Computational Biology Group, Institute of Infectious Disease and Molecular Medicine University of Cape Town, Private Bag, Rondebosch 7701, South Africa. konrad@cbio.uct.ac.za

Bioinformatics (Oxford, England)
|August 10, 2006
PubMed
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This study introduces a new phylogenetic method to accurately detect positive Darwinian selection in recombining pathogen genomes. The method significantly reduces false positives, improving evolutionary analysis for viruses like HIV-1.

Area of Science:

  • Evolutionary Biology
  • Genomics
  • Bioinformatics

Background:

  • Detecting positive Darwinian selection is crucial for understanding pathogen evolution.
  • Standard phylogenetic methods yield misleading results for recombining viral sequences due to frequent recombination.
  • Accurate selection detection provides insights into pathogen adaptation and virulence.

Purpose of the Study:

  • To develop a maximum likelihood inference method for detecting positive selection robust to recombination.
  • To improve the accuracy and reliability of phylogenetic analyses in the presence of recombination.
  • To provide a reliable tool for studying the evolution of pathogens, especially viruses.

Main Methods:

  • Developed a maximum likelihood method allowing dynamic tree topologies and branch lengths across recombination breakpoints.

Related Experiment Videos

  • Incorporated site-specific synonymous substitution rate variation.
  • Validated the method using simulations and applied it to HIV-1 datasets.

    • Main Results:

    • The proposed method significantly reduces false positive rates in the presence of recombination, even in extreme cases.
    • Simulations showed the method maintains high statistical power while controlling false positives.
    • Applied to HIV-1 env and gag genes, detecting positive selection in env but not gag, resolving previous ambiguities.

    Conclusions:

    • The new method offers a robust approach to infer positive selection in recombining sequences.
    • It overcomes limitations of standard phylogenetic methods when applied to viruses.
    • The approach enhances the study of viral evolution and adaptation.