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.
Kosakovsky Pond
Sergei L
SL
Department of Pathology, University of California, San Diego, CA, USA. spond@ucsd.edu
Poon
Art F Y
AF
Leigh Brown
Andrew J
AJ
Frost
Simon D W
SD
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