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Nature: A synchronized global sweep of the internal genes of modern avian influenza virus

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  • Nature: A synchronized global sweep of the internal genes of modern avian influenza virus

    A synchronized global sweep of the internal genes of modern avian influenza virus

    Michael Worobey1
    Guan-Zhu Han1
    Andrew Rambaut2, 3


    Nature
    (2014)
    doi:10.1038/nature13016



    Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health1. However, the factors that mediate the emergence of RNA viruses such as influenza A virus (IAV) are still incompletely understood2, 3. Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts3, 4, 5, 6, 7, 8. Here we show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including ‘relaxed’ molecular clock models9, can be positively misleading. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds—as well as those from humans, swine and the equine H3N8 lineage—sharing an ancestor with them in the mid to late 1800s. Moreover, major western and eastern hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a clear resolution of evolutionary patterns and processes in IAV, including the flow of viral genes and genomes within and between host lineages.



  • #2
    Re: Nature: A synchronized global sweep of the internal genes of modern avian influenza virus

    Study revives bird origin for 1918 flu pandemic

    Model also links avian influenza strains to deadly horse flu.

    Hannah Hoag

    16 February 2014


    The virus that caused the 1918 influenza pandemic likely sprang from North American domestic and wild birds, not from the mixing of human and swine viruses. A study published today in Nature1 reconstructs the origins of influenza A virus and traces its evolution and flow through different animal hosts over two centuries.

    full article



    Comment


    • #3
      I can't verify that European and American PB2 may have a common ancester in ~1888.
      Looks more like ~1800 to me. Maybe there is no clear "clock" in mallards with waterborne transmission
      and possible survival in the environment for prolonged time. (see the slow evolution thread ...)



      [but that picture confirms the American origin of the 1918-PB2 and the
      Eurasian origin of the 1925-PB2]
      [also the special role of the Alaska viruses (Eurasian or slow evolution i.e. murres from 1976)]





      ---------------edit---------------
      well, it could be that there are already so many mutations that the further
      increase becomes asymptotic, due to lack of new positions
      1918-2007human - 240 differences
      1918-2006 swine - 316 differences
      2007human - 2006swine = 380 differences
      1918-1925 - 294 differences
      1918-2013:341,1925-2013:292
      mallards, PB2, Eurasia , 30 years = 170 differences
      15 years = 100 differences
      I must have estimated this earlier in other threads ...

      ----------edit 2015/03/19-----
      I examined this for the human-1912-swine lineage :
      http://magictour.free.fr/swhu200.GIF




      -----------------------------------------------------------from the paper:-------------------------------------------------
      Analyses of alignments of full-length segments encoding the IVA (influenza A virus)
      polymerase proteins (PB2, PB1, PA);
      the hemagglutinin (HA) surface glycoprotein subtypes H1, H3, and H7;
      the nucleocapsid protein (NP);
      the neuraminidase (NA) surface glycoprotein subtypes N1, N8, and N7;
      the matrix proteins (M1/2); and the
      nonstructural proteins (NS1/2)
      show how the HSLC (host-specific local clock) model can outperform those assuming
      a single distribution of rates across hosts.

      Unlike previous approaches17 (Extended Data Fig. 2), the HSLC model provides consistent,
      statistically strong evidence that the 1918 pandemic virus?fs PB2, PB1, PA, NP, M1/2, and
      perhaps NS1/2 arose from the Western Hemisphere AIV (avian influenza virus) lineage (Figs. 2 & S1).

      We constructed sequence alignments using all available full-segment IVA
      sequences encoding PB2, PB1, PA, HA (H1, H3, H7), NP, NA (N1, N7, N8), M1/2, and
      NS1/2 from birds, horses, pigs, humans, and fruit bats.

      A total of >80,000 influenza A virus full-length genome segment nucleotide sequences
      encoding PB2, PB1, PA, HA (H1, H3, H7), NP, NA (N1, N7, N8), M1/2, and NS1/2 were
      retrieved from the NCBI Influenza Virus Resource31

      In PB2, NP, M1/2, and NS1/2, the sizeable, distinct viral clades from hosts in the order
      Charadriiformes (gulls, shorebirds, and relatives) were allowed a distinct clock rate

      The estimated origin dates of the equine H7N7 genes based on U
      content values were:
      PB2 1548[1533-1574];
      PB1 1842[1816-1877];
      PA 1819[1795-1842];
      H7 1880[1878-1884];
      NP 1785[1747-1823];
      N7 1387[1373-1413];
      M1/2 1801[1724-1879];
      NS1/2 1835[1810-1861]).

      The timelines of the trees are also similar, with
      the most recent common ancestor (MRCA) of the equine H7N7 and avian lineages (node 1)
      dated between the 1830s and 1870s, and the MRCA of all avian strains (node 2) dated
      between the 1860s and 1890s.

      Node 1*
      Node 2*
      Data set from Figure 2 (GTR (general time reversible ) model)
      PB2,1854 [1843-1864],1888 [1883-1892]
      PB1,1851 [1840-1860],1868 [1861-1875]
      PA,1862 [1853-1873],1887 [1881-1892]
      H7,1854 [1839-1867],1880 [1868-1890]
      NP,1869 [1860-1879],1885 [1879-1891]
      N7,1836 [1811-1860],1863 [1842-1878]
      M1/2,1879 [1866-1890],1897 [1890-1904]
      NS1/2,1862 [1845-1878],1899 [1886-1908]

      Data set from Figure 2 (SRD (separation-related distress) + galliform clock)
      PB2,1851 [1840-1862],1887 [1882-1891]
      PB1,1849 [1839-1859],1866 [1859-1873]
      PA,1858 [1847-1866],1886 [1881-1891]
      H7,1853 [1839-1867],1881 [1870-1891]
      NP,1868 [1857-1877],1883 [1877-1890]
      N7,1843 [1819-1866],1866 [1848-1881]
      M1/2,1876 [1863-1887],1897 [1891-1905]
      NS1/2,1858 [1839-1874],1893 [1880-1905]

      Subsampled sequences from Figure 2 data (internal genes, SRD)
      PB2,1856 [1844-1868],1886 [1880-1892]
      PB1,1853 [1842-1862],N/A??
      PA,1865 [1853-1876],1881 [1874-1888]
      NP,1872 [1864-1879],1875 [1868-1882]
      M1/2,1876 [1860-1889],1886 [1874-1896]
      NS1/2,1846 [1821-1867],1886 [1870-1898]

      Same data set as Figure 2, except using 3rd codon position sites only (SRD +
      galliform clock)
      PB2,1856 [1848-1863],1881 [1873-1887]
      PB1,1854 [1844-1865],N/A??
      PA,1857 [1844-1869],1884 [1879-1890]
      H7,1851 [1831-1868],1866 [1848-1881]
      NP,1870 [1861-1879],1883 [1875-1890]
      N7,1836 [1806-1860],1852 [1828-1875]
      M1/2,1887 [1875-1898],1899 [1891-1906]
      NS1/2,1859 [1840-1877],1899 [1886-1907]

      *See Fig. 2
      ??Node not present on MCC (maximum clade credibility) tree
      Extended Data Table 2
      Complete or partial sweeps of Eastern Hemisphere-
      origin AIV internal genes across Western Hemisphere
      AIV in recent decades
      Total No. of Western Hemisphere
      AIV full-length
      sequences, 2009-2013
      No. in West-1 clade*
      No. in West-2 clade
      No. in West-3 clade
      PB1,1059,0 (0 %)*,1059 (100%)??,0 (0%)??
      PA,1052,1 (0.1%)*,420 (39.9%)??,631 (60.0%)?a
      NP,886,12 (1.4%)*,863 (97.4%)??,N/A
      NS1/2,560??,6 (1.1%)*,554 (98.9%)#,N/A

      *This is the pre-20th century Western Hemisphere AIV lineage (see Fig. 2 for clade designations).
      ??Migrated from Eastern Hemisphere after ~1945 and before ~1955.
      ??Migrated from Eastern Hemisphere after ~1945 and before ~1960.
      ??Migrated from Eastern Hemisphere after ~1921 and before ~1940.
      ?aMigrated from Eastern Hemisphere after ~1965 and before ~1969.
      ??Migrated from Eastern Hemisphere after ~1940 and before ~1945.
      #Migrated from Eastern Hemisphere after ~1928 and before ~1940.
      **NS A lineage sequences only; there were an additional 262 NS B lineage sequences
      (30% of 822 total NS sequences).
      Last edited by gsgs; March 19, 2015, 12:44 PM.
      I'm interested in expert panflu damage estimates
      my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

      Comment


      • #4
        We used substitution model parameters and host-specific rate ratios representative of real multi-host
        IVA data sets. ‘Equine’, ‘human’, and ‘avian’ clades were set to evolve at relative rates of 1:2:3,
        respectively, to cover the empirically observed range of rates in real IVA data sets (see Fig.2).

        /* [this 1:2:3 is new. It has never been suggested or observed before, including the papers which they cite.
        Do they really mean, influenza mutates in birds 3 times faster(more) than in horses ??
        It seems so, afaicu. I cannot verify this, see table below.]
        figure 2.a shows a plylo-tree, I don't have the data from which it is calculated.
        {well, there is some data available but it is subject to the lengthy DRYAD terms of service,
        which I'm not willing to read} Together with 4 colored mountains supposedly showing mutations
        per site per year with peaks at ~1.6e-3 for human, 2.0e-3 for horses, 2.4e-3 for birds (ducks ?),
        2.6e-3 for swine .
        While figure 2.b suggests peaks at 1.6e-3 for equine, 1.7e-3 for human, 2.2e-3 for ducks,
        2.7e-3 for swine.] */

        Simulation with unequal sampling across clades, with ‘fast’ clade
        (‘avian’) sequences over-represented. (The model tree was identical to that in Fig. 1a except
        for the unequal number of sequences from the different clades as shown.) d, Simulation with
        ‘slow’ clade (‘equine’) sequences over-represented. Unlike the HSLC model, root date
        estimates are systematically biased under both strict and relaxed clock models and are
        strongly influenced by the balance of ‘fast-clade’ and ‘slow-clade’ sequences sampled.

        For the internal genes the equine H7N7 rate was linked to the equine H3N8 rate because there
        were not enough sequences to calibrate H7N7 on its own. The similarity between the results for
        the internal gene analyses to the results for H7 and N7, where there were enough equine
        H7N7 sequences to calibrate the rate, suggests that linking H7N7 to the H3N8 rates in those
        segments was a valid approach.

        ---------------------------------------------------------------------------------------------------------------------
        nucleotide differences in the 8 segments:

        12 >Index/2009/Egypt/Iowa(H3N2)
        1957: 17:190,229,163,---,125,189, 52, 69 = 1273e ~ 1.87e-3 (52)
        1968: 1:161,176,159,224,129,165, 47, 54 = 1115 ~ 2.07e-3 (41)
        1972: 2:128,161,116,197, 98,133, 43, 46 = 922 ~ 1.90e-3 (37)
        1979: 3:107,132, 96,163, 80,117, 36, 30 = 761 ~ 1.93e-3 (30)

        1 >A/equine/Miami/1/1963(H3N8)
        2008: 1:141,162,157,153, 93,111, 38, 35 = 890 ~ 1.51e-3 (45)
        2013: 1:155,172,174,165, 97,129, 43, 39 = 974 ~ 1.49e-3 (50)

        3 >1979//,4199,THA,A/Bangkok/01/79(H3N2)
        1983: 4: 16, 18, 15, 28, 18, 19, 8, 9 = 135 ~ 2.57e-3 (04)
        1989: 5: 37, 53, 43, 59, 32, 45, 13, 13 = 295 ~ 2.25e-3 (10)
        1997: 6: 69, 93, 70,104, 48, 78, 21, 18 = 501 ~ 2.12e-3 (18)
        2003: 7: 94,111, 84,137, 61,103, 31, 24 = 645 ~ 2.05e-3 (24)
        2009: 12:107,132, 96,163, 80,117, 36, 30
        2007: 13: 99,119, 93,157, 77,112, 33, 27
        2002: 18: 89,104, 82,134, 59,100, 30, 24
        2003: 19: 94,107, 83,136, 61,104, 33, 24
        2003: 20: 94,109, 96,137, 60, 94, 29, 23
        2012: 25:120,135,107,176, 83,127, 43, 33 = 824 ~ 1.90e-3 (33)


        Code:
          [FONT=Arial][SIZE=10px]1 >A/Brevig Mission/1/1918(H1N1)
        6 >A/pintail duck/ALB/628/1979/08/13/
        241,205,286, 0,182, 0, 85, 42 = 1509 ~< 1.89e-3 (>49)
        7 >A/turkey/Ontario/6118/1968///
        234,194,174, 0,189, 0, 52, 30 = 1236 ~< 1.93e-3 (>50)
        8 >A/turkey/Ontario/7732/1966///
        230,182, 0, 0,190, 0, 52, 32 = 1240 ~< 1.97e-3 (<48)
        11 >A/duck/Manitoba_KF/1953(H10N7)
        212,166,272, 0,186, 0, 43, 33 =[/SIZE][/FONT]
        Code:
          [FONT=Arial][SIZE=10px] >A/duck/LA/17G/1987,1987//,H3N8[/SIZE][/FONT]
          [FONT=Arial][SIZE=10px]10 >A/cinnamon teal/California/44287-325/2007,2007/01/27,H3N8
        105,103,108, 74, 80, 66, 32, 27 = 595 ~ 2.27e-3 (20)
        20 >A/pekin duck/California/P30/2006,2006/03/06,H4N2
        90,112,103,---, 79,---, 31, 28 = 625 ~ 2.51e-3 (19)[/SIZE][/FONT]
        >A/Index Qinghai,2005/02/01,China,H5N1,Avian
        25 >A/chicken/Egypt/M7217B/2013,2013/01/31,Egypt,H5N1,Avian
        2013: 69, 62, 52, 43, 50, 41, 17, 26 = 360 ~ 3.4e-3 (08)

        but in wild birds it could be different. (smaller mutation rate)
        And we have examples of slow evolution in birds (mallards ?)
        and then especially, there are almost no non-synonymous mutations
        in the inner segments in mallards,pintails,teals etc. (the main reservoir)

        ------------------------
        actually I think the 2:3 for human:avian may be ~right
        but not 1:2 for equine:human
        Last edited by gsgs; March 19, 2015, 12:51 PM.
        I'm interested in expert panflu damage estimates
        my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

        Comment


        • #5
          mutation rates:








          I was surprised that it's so slow in horses

          [to do: h3n8 since 1968, h2n2, h1n1 since 1918,1977 , swine h1n1 since 1918, euroswine since 1978
          triple reassortant swine since 1997, h5n1 since 2003, h9n2 since 1995, 17g since 1987, h5n2 since 1985,
          h5n8 since 2014, h7n9 since 2013, equine h7n7 since 1956, swine h3n2
          better maybe: only synonymous mutations]


          I think the mutation rate depends more on the strain
          rather than on the host. It's higher in new, successful
          (pandemic,panzootic) strains and in strains
          that reassort much (==> need to adapt the
          other segments with mutations)
          It's also higher in HA and NA in humans, where there is
          antigenic pressure from immunity.
          This pressure also exists in birds, but birds live shorter
          and there are ample HAs to "choose" from.
          It's easier for the flu in wild birds to switch an
          entire HA than to evade immunity by mutating.
          ?@
          ?@
          ?@
          H3N2.Human,1972,1.96e-3(28)
          H3N2,Human,1972,2.40e-3(09)
          H1N1,Swine,1979,1.90e-3(34)
          H1N1,Swine,1979,2.05e-3(26)
          H123,Human,<1919,1.29e-3(82+) ,13578 only
          H123,Human,1933+,1.38e-3(28) ,13578 only
          H123,Human,<1919,1.61e-3(52+) ,13578 only
          H123,Human,<1919,2.42e-3(16+) ,13578 only
          H3N8,Equine,1959,1.41e-3(54)
          H3N8,Equine,1977+,1.27e-3(18)
          H3N8,Equine,1978,1.75e-3(18)
          H1N1,Human,2009,3.04e-3(05)
          H1N1,Hu+Sw,1914,3.81e-3(23) ,1 only
          H1N1,Hu+Sw,1914,3.06e-3(43)
          H1N1,Human,1918,1.83e-3(54)
          H1N1,Human,1918,1.91e-3(46)
          H1N1,Swine,1918,1.54e-3(87)
          H1N1,Swine,1918,1.55e-3(58)
          H5N1qh,Avian,2005,3.44e-3(08)
          H3N817g,Avian,1987,2.26e-3(20)
          ?@
          20y
          Hu,2.1,2.0,2.2
          Sw,2.1,
          Eq,1.7,
          Av,2.3,
          50y
          Hu,1.7,1.9
          Eq,1.4
          ?@
          Last edited by gsgs; March 22, 2015, 10:15 AM.
          I'm interested in expert panflu damage estimates
          my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

          Comment

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