A maximum likelihood method for detecting directional evolution in protein sequences and its application to influenza A virus.
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.
Department of Pathology, University of California, San Diego, CA, USA. spond@ucsd.edu
Sergei L
SL
Kosakovsky Pond
Art F Y
AF
Poon
Andrew J
AJ
Leigh Brown
Simon D W
SD
Frost
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D003198:Computer Simulation; D019143:Evolution, Molecular; D005814:Genes, Viral; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics*; D009980:Influenza A virus / Q000235:genetics; D016013:Likelihood Functions; D008957:Models, Genetic; D015233:Models, Statistical; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics*
D014764:Viral Proteins