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Review
. 2004 Mar;12(3):106-11.
doi: 10.1016/j.tim.2004.01.005.

Phylogenomics and bioinformatics of SARS-CoV

Pietro Liò  1 , Nick Goldman
Affiliations
Review

Phylogenomics and bioinformatics of SARS-CoV

Pietro Liò et al. Trends Microbiol. 2004 Mar.

Abstract

Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. The topology and branch lengths of the phylogenetic relationships among the family Coronaviridae, including SARS-CoV, have been estimated using the replicase polyprotein. The spike protein fragments S1 (involved in receptor-binding) and S2 (involved in membrane fusion) have been found to have different mutation rates. Fragment S1 can be further divided into two regions (S1A, which comprises approximately the first 400 nucleotides, and S1B, comprising the next 280) that also show different rates of mutation. The phylogeny presented on the basis of S1B shows that SARS-CoV is closely related to MHV (murine hepatitis virus), which is known to bind the murine receptor CEACAM1. The predicted structure, accessibility and mutation rate of the S1B region is also presented. Because anti-SARS drugs based on S2 heptads have short half-lives and are difficult to manufacture, our findings suggest that the S1B region might be of interest for anti-SARS drug discovery.

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Figures

Figure 1
Figure 1
Maximum likelihood tree produced using Passml-TM based on the replicase proteins from members of of the order Nidovirales, comprising 17 coronaviruses [from group 1: human coronavirus 229E (HCoV-229E), porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), canine coronavirus (CCoV) and feline coronavirus (FCoV); from group 2: bovine coronavirus (BCoV), rat coronavirus (RtCoV), murine hepatitis virus (MHV), human coronavirus OC43 (HCoV-OC43) and porcine hemagglutinating encephalomyelitis virus (HEV); intermediate between groups 1 and 2: avian infectious bronchitis virus (IBV) and turkey coronavirus (TCV); and SARS-CoVs from strains Tor2, bj01, bj02, bj03 and CUHKW1], one torovirus (Breda) and one okavirus (yellow head virus, YH). The scale bar indicates evolutionary divergence corresponding to a mean of 0.1 amino acid replacements per site.
Figure 2
Figure 2
(a) Schematic diagram of the spike protein gene showing S1A, S1B (faster evolving) and S2 (conserved) regions. The inferred transmembrane region is represented in black. The heptad repeats (r) and cysteine-rich domain (c) are also shown. Maximum likelihood trees of the (b) S1B and (c) S2 regions of the spike protein. The scale bars indicate the mean numbers of amino acid replacements per site. Species used include 17 coronaviruses [from group 1: human coronavirus 229E (HCoV-229E), porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), canine coronavirus (CCoV) and feline coronavirus (FCoV); from group 2: bovine coronavirus (BCoV), rat coronavirus (RtCoV), murine hepatitis virus (MHV), human coronavirus OC43 (HCoV-OC43) and porcine hemagglutinating encephalomyelitis virus (HEV); intermediate between groups 1 and 2: avian infectious bronchitis virus (IBV) and turkey coronavirus (TCV); and SARS-CoVs from strains Tor2, bj01, bj02, bj03 and CUHKW1], one torovirus (Breda) and one okavirus (yellow head virus, YH). Coloured areas indicate coronavirus groups 1 (blue) and 2 (yellow). (d) Predicted structure and mutation rate for the SARS-CoV S1B region. Secondary structure has been predicted (row Pred) in three classes: helix (H), sheet (E) and coil (C). Accessibility has been predicted (row Acc) in three classes: buried (b), exposed (e) and intermediate (i). Mutation rates (row Mut) are partitioned into eight classes (classes 1–8 have relative rates of evolution 0.10, 0.27, 0.44, 0.64, 0.88, 1.19, 1.65 and 2.83, respectively), inferred using the empirical Bayes method . The sequence homologous to the region 522–744 of the TGEV spike protein is shown in red. Maximum likelihood trees and mutation rate analyses were computed using Passml-TM .
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References

    1. Whelan S. Molecular phylogenetics: state-of-the-art methods for looking into the past. Trends Genet. 2001;17:262–272. - PubMed
    1. Marra M.A. The genome sequence of the SARS-associated coronavirus. Science. 2003;300:1399–1404. - PubMed
    1. Rota P.A. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. 2003;300:1394–1399. - PubMed
    1. Butler P.J.G. Self-assembly of tobacco mosaic virus: the role of an intermediate aggregate in generating both specificity and speed. Philos. Trans. R. Soc. Lond. B Biol. Sci. 1999;354:537–550. - PMC - PubMed
    1. Russell R.B. Recognition of analogous and homologous protein folds: analysis of sequence and structure conservation. J. Mol. Biol. 1997;269:423–439. - PubMed

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