title: Differential stepwise evolution of SARS coronavirus functional proteins in different host species.
abstract: BACKGROUND
  SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known.
  
  
  RESULTS
  We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified.
  
  
  CONCLUSIONS
  This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.
authors.affiliation: School of Life Science, East China Normal University, Shanghai, 200062, PR China. xtang@pitt.edu
authors.forename: Xianchun
authors.initials: X
authors.lastname: Tang
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Nikos
authors.initials: N
authors.lastname: Vasilakis
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhengli
authors.initials: Z
authors.lastname: Shi
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhong
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.forename: Shuyi
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002685:Chiroptera / Q000821:virology; D019143:Evolution, Molecular; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D008957:Models, Genetic; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics*; D012641:Selection, Genetic; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D045169:Severe Acute Respiratory Syndrome / Q000821:virology; D013045:Species Specificity; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D012367:RNA, Viral; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D012324:RNA-Dependent RNA Polymerase