title: Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.
abstract: Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.
authors.affiliation: Butantan Institute, Virology Branch, Butantã, São Paulo, Brazil.
authors.forename: Viviane F
authors.initials: VF
authors.lastname: Botosso
authors.forename: Paolo M de A
authors.initials: PM
authors.lastname: Zanotto
authors.forename: Mirthes
authors.initials: M
authors.lastname: Ueda
authors.forename: Eurico
authors.initials: E
authors.lastname: Arruda
authors.forename: Alfredo E
authors.initials: AE
authors.lastname: Gilio
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Vieira
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Stewien
authors.forename: Teresa C T
authors.initials: TC
authors.lastname: Peret
authors.forename: Leda F
authors.initials: LF
authors.lastname: Jamal
authors.forename: Maria I de M C
authors.initials: MI
authors.lastname: Pardini
authors.forename: João R R
authors.initials: JR
authors.lastname: Pinho
authors.forename: Eduardo
authors.initials: E
authors.lastname: Massad
authors.forename: Osvaldo A
authors.initials: OA
authors.lastname: Sant'anna
authors.forename: Eddie C
authors.initials: EC
authors.lastname: Holmes
authors.forename: Edison L
authors.initials: EL
authors.lastname: Durigon
mesh_terms: D019943:Amino Acid Substitution; D000939:Epitopes; D019143:Evolution, Molecular; D019204:GTP-Binding Proteins / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010802:Phylogeny; D012136:Respiratory Syncytial Viruses / Q000235:genetics*; D012141:Respiratory Tract Infections; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D000939:Epitopes; D014764:Viral Proteins; D019204:GTP-Binding Proteins