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Identifying changes in selective constraints: host shifts in influenza.

Tamuri AU, Dos Reis M, Hay AJ, Goldstein RA - PLoS Comput. Biol. (2009)

Bottom Line: We use a sitewise non-homogeneous phylogenetic model that explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations.Identification of the sequence changes necessary for host shifts would help us predict the pandemic potential of various strains.The method is of broad applicability to investigating changes in selective constraints when the timing of the changes is known.

View Article: PubMed Central - PubMed

Affiliation: National Institute for Medical Research, London, United Kingdom.

ABSTRACT
The natural reservoir of Influenza A is waterfowl. Normally, waterfowl viruses are not adapted to infect and spread in the human population. Sometimes, through reassortment or through whole host shift events, genetic material from waterfowl viruses is introduced into the human population causing worldwide pandemics. Identifying which mutations allow viruses from avian origin to spread successfully in the human population is of great importance in predicting and controlling influenza pandemics. Here we describe a novel approach to identify such mutations. We use a sitewise non-homogeneous phylogenetic model that explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations. We identify 172 amino acid sites with strong support and 518 sites with moderate support of different selection constraints in human and avian viruses. The sites that we identify provide an invaluable resource to experimental virologists studying adaptation of avian flu viruses to the human host. Identification of the sequence changes necessary for host shifts would help us predict the pandemic potential of various strains. The method is of broad applicability to investigating changes in selective constraints when the timing of the changes is known.

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Selective constraint strengths for viral sites in Avian and Human influenza.Strength of selective constraints (measured as d, as described in Eqn. 5), for viral sites identified (FDR<0.05) as under different selective constraints in avian and human hosts. Colour coding refers to specific gene: HA (red), NA (blue), M1 (black), M2 (brown), NP (green), NS1 (orange), PA (cyan), PB1 (purple), PB2 (magenta). Selective sites are labelled.
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pcbi-1000564-g004: Selective constraint strengths for viral sites in Avian and Human influenza.Strength of selective constraints (measured as d, as described in Eqn. 5), for viral sites identified (FDR<0.05) as under different selective constraints in avian and human hosts. Colour coding refers to specific gene: HA (red), NA (blue), M1 (black), M2 (brown), NP (green), NS1 (orange), PA (cyan), PB1 (purple), PB2 (magenta). Selective sites are labelled.

Mentions: The theoretically predicted weak dependence of ν on selective pressure and the lack of statistical support for host-dependent values of this parameter indicate that ν is not a good measure of the degree of selective constraints. To generate a more appropriate measure, we calculated the relative entropy between the equilibrium frequencies and what would be expected under no selection, π0, estimating the latter by averaging the amino acid frequencies over our entire database. This measure of selective constraint magnitudes for the various sites in avian and human hosts are presented in Table 1, Supporting Table S1, and in Figure 4.


Identifying changes in selective constraints: host shifts in influenza.

Tamuri AU, Dos Reis M, Hay AJ, Goldstein RA - PLoS Comput. Biol. (2009)

Selective constraint strengths for viral sites in Avian and Human influenza.Strength of selective constraints (measured as d, as described in Eqn. 5), for viral sites identified (FDR<0.05) as under different selective constraints in avian and human hosts. Colour coding refers to specific gene: HA (red), NA (blue), M1 (black), M2 (brown), NP (green), NS1 (orange), PA (cyan), PB1 (purple), PB2 (magenta). Selective sites are labelled.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2770840&req=5

pcbi-1000564-g004: Selective constraint strengths for viral sites in Avian and Human influenza.Strength of selective constraints (measured as d, as described in Eqn. 5), for viral sites identified (FDR<0.05) as under different selective constraints in avian and human hosts. Colour coding refers to specific gene: HA (red), NA (blue), M1 (black), M2 (brown), NP (green), NS1 (orange), PA (cyan), PB1 (purple), PB2 (magenta). Selective sites are labelled.
Mentions: The theoretically predicted weak dependence of ν on selective pressure and the lack of statistical support for host-dependent values of this parameter indicate that ν is not a good measure of the degree of selective constraints. To generate a more appropriate measure, we calculated the relative entropy between the equilibrium frequencies and what would be expected under no selection, π0, estimating the latter by averaging the amino acid frequencies over our entire database. This measure of selective constraint magnitudes for the various sites in avian and human hosts are presented in Table 1, Supporting Table S1, and in Figure 4.

Bottom Line: We use a sitewise non-homogeneous phylogenetic model that explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations.Identification of the sequence changes necessary for host shifts would help us predict the pandemic potential of various strains.The method is of broad applicability to investigating changes in selective constraints when the timing of the changes is known.

View Article: PubMed Central - PubMed

Affiliation: National Institute for Medical Research, London, United Kingdom.

ABSTRACT
The natural reservoir of Influenza A is waterfowl. Normally, waterfowl viruses are not adapted to infect and spread in the human population. Sometimes, through reassortment or through whole host shift events, genetic material from waterfowl viruses is introduced into the human population causing worldwide pandemics. Identifying which mutations allow viruses from avian origin to spread successfully in the human population is of great importance in predicting and controlling influenza pandemics. Here we describe a novel approach to identify such mutations. We use a sitewise non-homogeneous phylogenetic model that explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations. We identify 172 amino acid sites with strong support and 518 sites with moderate support of different selection constraints in human and avian viruses. The sites that we identify provide an invaluable resource to experimental virologists studying adaptation of avian flu viruses to the human host. Identification of the sequence changes necessary for host shifts would help us predict the pandemic potential of various strains. The method is of broad applicability to investigating changes in selective constraints when the timing of the changes is known.

Show MeSH
Related in: MedlinePlus