title: Different rates of (non-)synonymous mutations in astrovirus genes; correlation with gene function.
abstract: BACKGROUND
  Complete genome sequences of the Astroviridae include human, non-human mammalian and avian species. A consensus topology of astroviruses has been derived from nucleotide substitutions in the full-length genomes and from non-synonymous nucleotide substitutions in each of the three ORFs. Analyses of synonymous substitutions displayed a loss of tree structure, suggesting either saturation of the substitution model or a deviant pattern of synonymous substitutions in certain virus species.
  
  
  RESULTS
  We analyzed the complete Astroviridae family for the inference of adaptive molecular evolution at sites and in branches. High rates of synonymous mutations are observed among the non-human virus species. Deviant patterns of synonymous substitutions are found in the capsid structural genes. Purifying selection is a dominant force among all astrovirus genes and only few codon sites showed values for the dN/dS ratio that may indicate site-specific molecular adaptation during virus evolution. One of these sites is the glycine residue of a RGD motif in ORF2 of human astrovirus serotype 1. RGD or similar integrin recognition motifs are present in nearly all astrovirus species.
  
  
  CONCLUSIONS
  Phylogenetic analysis directed by maximum likelihood approximation allows the inclusion of significantly more evolutionary history and thereby, improves the estimation of dN and dS. Sites with enhanced values for dN/dS are prominent at domains in charge of environmental communication (f.i. VP27 and domain 4 in ORF1a) more than at domains dedicated to intrinsic virus functions (f.i. VP34 and ORF1b (the virus polymerase)). Integrin recognition may play a key role in astrovirus to target cell attachment.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, The Netherlands. f.j.vanhemert@amc.uva.nl
authors.forename: Formijn J
authors.initials: FJ
authors.lastname: van Hemert
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Lukashov
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
mesh_terms: D000818:Animals; D019200:Astroviridae / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D001717:Birds; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D002415:Cats; D019143:Evolution, Molecular; D005814:Genes, Viral; D006801:Humans; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics; D012641:Selection, Genetic; D012756:Sheep; D013045:Species Specificity; D013552:Swine; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D014764:Viral Proteins