A maximum likelihood method for detecting directional evolution in protein sequences and its application to influenza A virus.

  • Pond S
  • Poon A
  • Brown A
 et al. 
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We develop a model-based phylogenetic maximum likelihood test for evidence of preferential substitution toward a given residue at individual positions of a protein alignment--directional evolution of protein sequences (DEPS). DEPS can identify both the target residue and sites evolving toward it, help detect selective sweeps and frequency-dependent selection--scenarios that confound most existing tests for selection, and achieve good power and accuracy on simulated data. We applied DEPS to alignments representing different genomic regions of influenza A virus (IAV), sampled from avian hosts (H5N1 serotype) and human hosts (H3N2 serotype), and identified multiple directionally evolving sites in 5/8 genomic segments of H5N1 and H3N2 IAV. We propose a simple descriptive classification of directionally evolving sites into 5 groups based on the temporal distribution of residue frequencies and document known functional correlates, such as immune escape or host adaptation.

Author-supplied keywords

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Computer Simulation
  • Evolution
  • Genes
  • Genetic
  • H3N2 Subtype
  • H3N2 Subtype: genetics
  • H5N1 Subtype
  • H5N1 Subtype: genetics
  • Humans
  • Influenza A Virus
  • Influenza A virus: genetics
  • Likelihood Functions
  • Models
  • Molecular
  • Polymorphism
  • Sequence Alignment
  • Statistical
  • Viral
  • Viral Proteins
  • Viral Proteins: genetics

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  • Sergei L K Pond

  • Art F Y Poon

  • Andrew J L Brown

  • Simon D W Frost

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