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Different rates of (non-)synonymous mutations in astrovirus genes; correlation with gene function.

van Hemert FJ, Lukashov VV, Berkhout B - Virol. J. (2007)

Bottom Line: Deviant patterns of synonymous substitutions are found in the capsid structural genes.Phylogenetic analysis directed by maximum likelihood approximation allows the inclusion of significantly more evolutionary history and thereby, improves the estimation of dN and dS.Integrin recognition may play a key role in astrovirus to target cell attachment.

View Article: PubMed Central - HTML - PubMed

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

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.

Conclusion: 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.

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Related in: MedlinePlus

PAML trees of non-synonymous (A) and synonymous (B) substitutions in ORF1a (left panel), ORF1b (middle panel) and ORF2 (right panel) of astrovirus. PAML trees have been constructed by decorating the topology supplied by the input treefile with the branch lengths estimated by means of PAML approximation. The scale bars indicate the relative extent of mutational rates as (non-) synonymous substitutions per (non-) synonymous site corrected for multiple hits at the same site.
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Figure 1: PAML trees of non-synonymous (A) and synonymous (B) substitutions in ORF1a (left panel), ORF1b (middle panel) and ORF2 (right panel) of astrovirus. PAML trees have been constructed by decorating the topology supplied by the input treefile with the branch lengths estimated by means of PAML approximation. The scale bars indicate the relative extent of mutational rates as (non-) synonymous substitutions per (non-) synonymous site corrected for multiple hits at the same site.

Mentions: The values for dN/dS of the branch model applied to the astrovirus ORFs are all far below the value of 1 (Table 1), by convention considered as the lower limit for positive selection. In fact, dN/dS values do not exceed 0.16, except for ORF2 in the cat and human4 isolates (0.1904 and 0.2610, respectively). Obviously, purifying selection is very dominant in branches specifying astrovirus species. The individual values of dN and dS may be more easily interpreted in a tree format (Fig 1) than as raw data in a table. Unrooted dN and dS trees are part of PAML's output and have been constructed by pasting the dN and dS values from Table 1 as branch length onto the amino acid tree topology supplied to PAML as input tree file.


Different rates of (non-)synonymous mutations in astrovirus genes; correlation with gene function.

van Hemert FJ, Lukashov VV, Berkhout B - Virol. J. (2007)

PAML trees of non-synonymous (A) and synonymous (B) substitutions in ORF1a (left panel), ORF1b (middle panel) and ORF2 (right panel) of astrovirus. PAML trees have been constructed by decorating the topology supplied by the input treefile with the branch lengths estimated by means of PAML approximation. The scale bars indicate the relative extent of mutational rates as (non-) synonymous substitutions per (non-) synonymous site corrected for multiple hits at the same site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1828050&req=5

Figure 1: PAML trees of non-synonymous (A) and synonymous (B) substitutions in ORF1a (left panel), ORF1b (middle panel) and ORF2 (right panel) of astrovirus. PAML trees have been constructed by decorating the topology supplied by the input treefile with the branch lengths estimated by means of PAML approximation. The scale bars indicate the relative extent of mutational rates as (non-) synonymous substitutions per (non-) synonymous site corrected for multiple hits at the same site.
Mentions: The values for dN/dS of the branch model applied to the astrovirus ORFs are all far below the value of 1 (Table 1), by convention considered as the lower limit for positive selection. In fact, dN/dS values do not exceed 0.16, except for ORF2 in the cat and human4 isolates (0.1904 and 0.2610, respectively). Obviously, purifying selection is very dominant in branches specifying astrovirus species. The individual values of dN and dS may be more easily interpreted in a tree format (Fig 1) than as raw data in a table. Unrooted dN and dS trees are part of PAML's output and have been constructed by pasting the dN and dS values from Table 1 as branch length onto the amino acid tree topology supplied to PAML as input tree file.

Bottom Line: Deviant patterns of synonymous substitutions are found in the capsid structural genes.Phylogenetic analysis directed by maximum likelihood approximation allows the inclusion of significantly more evolutionary history and thereby, improves the estimation of dN and dS.Integrin recognition may play a key role in astrovirus to target cell attachment.

View Article: PubMed Central - HTML - PubMed

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

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus