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Genome-wide networks of amino acid covariances are common among viruses.

ABSTRACT: Coordinated variation among positions in amino acid sequence alignments can reveal genetic dependencies at noncontiguous positions, but methods to assess these interactions are incompletely developed. Previously, we found genome-wide networks of covarying residue positions in the hepatitis C virus genome (R. Aurora, M. J. Donlin, N. A. Cannon, and J. E. Tavis, J. Clin. Invest. 119:225-236, 2009). Here, we asked whether such networks are present in a diverse set of viruses and, if so, what they may imply about viral biology. Viral sequences were obtained for 16 viruses in 13 species from 9 families. The entire viral coding potential for each virus was aligned, all possible amino acid covariances were identified using the observed-minus-expected-squared algorithm at a false-discovery rate of ?1%, and networks of covariances were assessed using standard methods. Covariances that spanned the viral coding potential were common in all viruses. In all cases, the covariances formed a single network that contained essentially all of the covariances. The hepatitis C virus networks had hub-and-spoke topologies, but all other networks had random topologies with an unusually large number of highly connected nodes. These results indicate that genome-wide networks of genetic associations and the coordinated evolution they imply are very common in viral genomes, that the networks rarely have the hub-and-spoke topology that dominates other biological networks, and that network topologies can vary substantially even within a given viral group. Five examples with hepatitis B virus and poliovirus are presented to illustrate how covariance network analysis can lead to inferences about viral biology.

SUBMITTER: Donlin MJ

PROVIDER: S-EPMC3302335 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Genome-wide networks of amino acid covariances are common among viruses.

Donlin Maureen J MJ Szeto Brandon B Gohara David W DW Aurora Rajeev R Tavis John E JE

Journal of virology 20120111 6

Coordinated variation among positions in amino acid sequence alignments can reveal genetic dependencies at noncontiguous positions, but methods to assess these interactions are incompletely developed. Previously, we found genome-wide networks of covarying residue positions in the hepatitis C virus genome (R. Aurora, M. J. Donlin, N. A. Cannon, and J. E. Tavis, J. Clin. Invest. 119:225-236, 2009). Here, we asked whether such networks are present in a diverse set of viruses and, if so, what they m ...[more]

PMID: 22238298

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Project description:As predicted by the nearly neutral model of evolution, numerous studies have shown that reduced N(e) accelerates the accumulation of slightly deleterious changes under genetic drift. While such studies have mostly focused on eukaryotes, bacteria also offer excellent models to explore the effects of N(e). Most notably, the genomes of host-dependent bacteria with small N(e) show signatures of genetic drift, including elevated K(a)/K(s). Here, I explore the utility of an alternative measure of selective constraint: the per-site rate of radical and conservative amino acid substitutions (D(r)/D(c)). I test the hypothesis that purifying selection against radical amino acid changes is less effective in two insect endosymbiont groups (Blochmannia of ants and Buchnera of aphids), compared to related gamma-Proteobacteria. Genome comparisons demonstrate a significant elevation in D(r)/D(c) in endosymbionts that affects the majority (66-79%) of shared orthologs examined. The elevation of D(r)/D(c) in endosymbionts affects all functional categories examined. Simulations indicate that D(r)/D(c) estimates are sensitive to codon frequencies and mutational parameters; however, estimation biases occur in the opposite direction as the patterns observed in genome comparisons, thereby making the inference of elevated D(r)/D(c) more conservative. Increased D(r)/D(c) and other signatures of genome degradation in endosymbionts are consistent with strong effects of genetic drift in their small populations, as well as linkage to selected sites in these asexual bacteria. While relaxed selection against radical substitutions may contribute, genome-wide processes such as genetic drift and linkage best explain the pervasive elevation in D(r)/D(c) across diverse functional categories that include basic cellular processes. Although the current study focuses on a few bacterial lineages, it suggests D(r)/D(c) is a useful gauge of selective constraint and may provide a valuable alternative to K(a)/K(s) when high sequence divergences preclude estimates of K(s). Broader application of D(r)/D(c) will benefit from approaches less prone to estimation biases.

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Genome-wide networks of amino acid covariances are common among viruses.

Publications

Genome-wide networks of amino acid covariances are common among viruses.

Similar Datasets

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