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  • antigenic avian influenza evolution is mainly restricted

    in several inner segments of influenza A we typically only see limited (~10)
    amino-acid changes in wild avian flu so that these segments are close to the calculated
    "index"-protein-sequence here:
    http://www.flutrackers.com/forum/sho...d.php?t=135205
    Synonymous changes are not affected and do occur at normal rates.

    No such restriction is observed in mammalean flu,
    which accumulates ~2.5*10^-3 nucleotide changes
    and ~4*10^-4 amino-acid changes per position per year.
    (6 nucleotide changes and 0.8 amino-acid changes in PB2 per year in humans)

    Poultry and swine are in the middle between mallards and humans
    wrt. protein-sequence-diversity = distance to the index :
    mallards-wild birds-poultry-swine-humans

    These index-like protein sequences occur independently
    on different genetical backgrounds. So do the exactly same
    (or more often: almost identical) protein sequences appears in
    North-American and Eurasian lineages where usually we do see
    separate evolution.
    But while the protein sequences are similar, there are many synonymous
    nucleotide differences, signalling a distant common ancestor.
    So, A/blue winged teal/Ohio/926/2002(H3N8)
    and A/mallard/Netherlands/2/2005(H4N2) have
    0 amino-acid differences (identical to the PB2-index)
    but have 343 nucleotide differences. There are other such examples and some
    viruses only have 0-3 differences to the index in all inner segments.

    This phenomenon can be visualized by plotting protein-differences
    vs. nucleotide-differences of pairs of avian flu segments:
    http://magictour.free.fr/panflu/seppp12.JPG
    The "clouds" approach the y-axis high above zero.
    The same picture for humans shows proportional acquisition of protein-
    and nucleotide-difference:
    http://magictour.free.fr/panflu/sepph3.GIF


    discussion here: http://www.flutrackers.com/forum/sho...d.php?t=135212

    or start a new thread

    ----------------------------------
    keywords:

    bird index , bird flu index , wild bird index , wild bird flu index , birdflu protein sequences index
    mallard index , mallard flu index , mallardflu index , avian influenza reference protein strain
    avian influenza reference index , gsgs , influenza , avian influenza , mallard influenza ,
    influenza in wild birds , poultry , mammals , hemagglutinin , neuraminidase , mutations ,
    mutation frequency , amino acid mutations , aminoacid mutations , protein mutations ,
    evolution , mutation rate , protein mutation rate
    I'm interested in expert panflu damage estimates
    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

  • #2
    Re: antigenic avian influenza evolution is mainly restricted

    ==============================================

    2360 avian segment1s by species

    1 average nucleotide-differences to other sequences in the list
    2 average protein-differences to other sequences in the list
    3 ratio 2/1
    4 average AT-score (proportion of A,T nucleotides)
    5 number of sequences from that species
    6 name of species


    Code:
    segment 1
       1    2    3     4    5    6 
    -----------------------------------
     1138  121  106  5487   14 widgeon
     1148  129  112  5483   51 shoveler
     1278  146  114  5486    3 tern
     1111  128  115  5472   73 pintail
     1136  131  115  5486  113 teal
     1134  133  117  5487  455 mallard
     1131  141  125  5487  146 turnstone
     1120  153  136  5508   31 stork
     1218  165  136  5513   19 shorebird
     1247  173  139  5525   47 gull
     1182  170  144  5517  327 Dk
     1252  185  148  5504  117 /Tk/
     1183  175  148  5508  141 
     1218  188  154  5491   35 fowl
     1276  199  156  5505    6 ostrich
     1159  185  160  5514   56 Gs
     1161  192  165  5539   33 swan
     1236  206  167  5542   33 /Qa
     1222  213  175  5548   10 pheasant
     1224  223  182  5530  623 Ck/
     1447  286  197  5693   10 stint
     1290  265  205  5574    5 avian

    ==============================================

    Code:
    segment 2
       1    2    3     4    5    6 
    --------------------------------
     858  115  134  5680  519 mallard
     859  117  136  5688  131 teal
     849  115  136  5693   72 pintail
     834  118  141  5691   68 shoveler
     865  124  144  5667  186 turnstone
     892  130  146  5660   19 shorebird
     886  130  147  5687   14 widgeon
     957  142  149  5626    5 tern
     961  146  152  5688   50 gull
     884  138  157  5736   32 stork
     919  146  159  5671  155 rest
     926  148  160  5673  397 Dk
    1115  182  163  5686   12 stint
     922  152  165  5700   36 swan
     913  152  167  5676   64 Gs
     901  152  169  5655   35 fowl
     930  159  171  5651  131 /Tk/
     944  174  184  5660   32 /Qa
     945  176  186  5630    7 ostrich
     952  186  195  5682  639 Ck/
     926  187  202  5664   13 pheasant
     991  245  247  5699    8 avian
    ==============================================

    Code:
    segment 3
       1    2    3     4    5    6 
    --------------------------------------
     944  179  190  5579   68 pintail
     987  188  190  5597  174 turnstone
    1011  195  192  5606   23 shorebird
     949  187  197  5568   14 widgeon
     958  191  199  5583  144 teal
     955  190  199  5585  532 mallard
     975  197  202  5572   62 shoveler
     956  193  202  5600   52 gull
     940  210  223  5612    5 tern
     916  217  236  5586  140 /Tk/
     862  209  242  5586    9 ostrich
     919  223  242  5603  167 
     891  222  249  5594  455 Dk
     994  250  251  5622   41 fowl
     835  218  261  5563   30 stork
     931  244  262  5595   13 pheasant
     883  232  263  5608   99 Gs
     863  229  265  5623   39 swan
     986  266  270  5652   66 avian
     947  257  271  5588   44 /Qa
     953  273  287  5613  708 Ck/
    1144  355  310  5735   11 stint
    Code:
    segment 5
    -----------------------------
     907  141  155  5231   45 shoveler
     891  141  158  5234   70 pintail
     886  143  161  5242  438 mallard
     890  146  164  5232   14 widgeon
     907  150  166  5242  102 teal
     925  160  173  5244  106 turnstone
     897  172  191  5171    5 tern
     921  178  193  5248  126 /Tk/
    1010  201  199  5246   21 shorebird
     881  176  200  5242  447 Dk
     864  173  200  5243   71 Gs
     896  188  209  5240  179 rest
     903  194  214  5278    4 ostrich
     867  187  215  5242   14 pheasant
     803  178  222  5229   26 stork
     975  216  222  5258   38 fowl
    1022  235  230  5313    4 avian
     918  218  237  5264  716 Ck/
     913  218  239  5253   42 /Qa
     852  208  244  5232   36 swan
    1204  296  245  5223   51 gull
    1477  595  402  5413   10 stint

    Code:
    segment 7 , M1+M2
    ------------------------------
     653  241  369  5096  119 turnstone
     738  272  369  5151   20 shorebird
     625  232  371  5089   45 shoveler
     637  237  372  5110  116 teal
     657  248  377  5115   72 pintail
     620  242  390  5105   14 widgeon
     646  253  391  5111  483 mallard
     786  310  395  5162   52 gull
     658  277  421  5081    5 ostrich
     699  303  434  5075    5 tern
     715  328  458  5122  147 /Tk/
     693  330  476  5126  428 Dk
     741  359  484  5124    7 avian
     715  351  491  5135  200 rest
     691  342  495  5140   76 Gs
     711  371  522  5160   15 pheasant
     996  524  526  5263    9 stint
     708  380  537  5183   35 swan
     792  430  543  5131   43 fowl
     753  417  554  5159  687 Ck/
     779  433  556  5164  115 /Qa
     734  478  651  5186   21 stork




    Code:
     1134  133  117  5487  455 mallard
     1182  170  144  5517  327 Dk
     1224  223  182  5530  623 Ck/
    
      858  115  134  5680  519 mallard
      926  148  160  5673  397 Dk
      952  186  195  5682  639 Ck/
    
      955  190  199  5585  532 mallard
      891  222  249  5594  455 Dk
      953  273  287  5613  708 Ck/
    
      886  143  161  5242  438 mallard
      881  176  200  5242  447 Dk
      918  218  237  5264  716 Ck/
    
      747  196  262  4965  485 mallard
      783  269  343  4979  428 Dk
      832  340  408  5021  686 Ck/


    (this could still be biased since most mallards are from America
    and most chickens from Eurasia)


    http://magictour.free.fr/panflu/spec1.GIF


    flu acquires more amino-acid mutations in poultry than
    in wild birds. It also increases the AT-score which is
    higher in human viruses than in avian ones.
    Wild bird amino-acid (=protein-) sequences are closer
    to the avian index.
    In poultry it mutates away from the index.
    We saw this in H5N1 and in H9N2.
    We have prolonged evolution of avian flu over decades
    in H9N2 and I assume we also had it in H5N1.

    There were several examples how low pathogenic H5 or H7
    became high pathogenic after some months of evolution in poultry stocks.

    So, it somehow "adapts" to humans by evolution in poultry.
    You may see poultry as a "mixing" vessel like swine.
    Poultry viruses like H9N2 or H5N1 should be more likely to
    cross to humans.
    The Dutch outbreak in 2003 was however caused by a
    wild-bird-like virus crossing over to poultry.
    These viruses should be less likely to persist and evolve for years.

    Poultry viruses and mammalean viruses usually die after decades,centuries
    when new viruses from the wild-bird reservoir are introduced
    on rare occasions and causing pandemics/panzootics and replace
    previousy existing strains.
    Evolution in the wild-bird reservoir seems to be superior despite
    the limited variation close to the bird-index.
    The reason could be increased reassortment i.e. with
    different HAs,NAs,NSs
    I'm interested in expert panflu damage estimates
    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

    Comment


    • #3
      Re: antigenic avian influenza evolution is mainly restricted

      1048 out of 2723 available full M1 protein sequences
      are identical to the index !

      This involves wild birds from distant places and times like:


      0 0 244 51 Dk/HK/34/1976(H3N2), 1976 , 10 , 3 , 0
      0 0 250 1381 gadwall/Altai/1328/07(H3N8)09, 2007 , 0 , 0 , 0
      0 0 251 1373 mallard/Czech Republic/12652/07(H4N6)08/06, 2007 , 3 , 0 , 0
      0 0 251 1957 mallard/MN/195/99(H4N6), 1999 , 3 , 0 , 0
      0 0 252 2341 pintail/Barrow/38/05(H8N4), 2005 , 6 , 0 , 0
      0 0 253 3 ostrich/South Africa/1991(H7N1), 1991 , 21 , 2 , 0
      0 0 253 33 pelican/Zambia/01/06(H3N6)08, 2006 , 0 , 3 , 0
      0 0 253 1102 Dk/England/1962(H4N8), 1962 , 10 , 0 , 0
      0 0 253 1152 Dk/Altai/1285/1991(H5N3)08/15, 1991 , 10 , 0 , 0
      0 0 253 1389 mallard/Czech Republic/14884-34/07(H9N2)09/24, 2007 , 3 , 0 , 0
      0 0 253 1427 Dk/Memphis/546/1974(H11N9), 1974 , 10 , 0 , 0
      0 0 253 1430 arctic tern/Alaska/300/1975(H5N3), 1975 , 4 , 0 , 0
      0 0 253 1442 murre/Alaska/305/1976(H1N6)01/01, 1976 , 0 , 0 , 0
      0 0 253 2664 Dk/NZL/31/1976(H4N6)01/01, 1976 , 10 , 0 , 0
      0 0 253 2667 shearwater/AUS/405/1978(H3N8)10/29, 1978 , 0 , 0 , 0
      0 0 253 2715 mallard/New Zealand/1615-17/04(H4N6), 2004 , 3 , 0 , 0
      0 0 253 2716 Dk/Tasmania/277/07(H7N2), 2007 , 10 , 0 , 0
      0 0 253 2719 Ck/Chile/4322/02(H7N3), 2002 , 1 , 0 , 0



      (1) promille out of (2) samples from species (3) have
      their M1 amino-acid sequence identical to the index.

      (1) (2) (3)
      ---------------------
      955 45 shoveler
      823 119 turnstone
      817 115 teal
      773 485 mallard
      666 72 pintail
      650 20 shorebird
      642 14 widgeon
      615 52 gull
      400 5 tern
      341 428 Dk
      338 201 rest
      300 150 /Tk/
      285 7 avian
      200 15 pheasant
      200 5 ostrich
      197 76 Gs
      186 43 fowl
      114 35 swan
      62 688 Ck/
      17 116 /Qa
      0 12 stint
      0 21 stork


      in poultry (and mammals) the virus slowly amino-mutates away from the index
      in wild birds apparantly the M1-index is so much advantageous that even
      small changes rarely survive.

      But there is one variation with 7 amino-acid mutations found in 35 wild birds in
      Minnessota/1998
      Ohio/1988
      Alberta/1985


      nucleotide-mutation picture of the 1048 amino-acid identical
      avian M1-regions is attached
      Attached Files
      I'm interested in expert panflu damage estimates
      my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

      Comment


      • #4
        Re: antigenic avian influenza evolution is mainly restricted

        I finally completed my "cloud" pictures for the 8 segments

        16 for segment 4, 9 for segment 6, 2 for segment 8,
        so 32 in total.
        Maybe we should (at least) further separate
        the American and Eurasian lineages for each of
        those 32 - that would make 64 and thus 64 index-strains.
        For the inner segments at the protein level the American
        and Eurasian indices should be very similar.


        each pixel is one pair of segments
        horizontal:synonymous differences
        vertical:nonsynonymous differences

        http://img46.yfrog.com/gal.php?g=sepp8.gif

        1: http://img682.yfrog.com/img682/9668/sepp1.gif
        2: http://img130.yfrog.com/img130/1489/sepp2.gif
        3: http://img697.yfrog.com/img697/6522/sepp3.gif
        4: http://img32.yfrog.com/img32/1519/sepp4.gif
        5: http://img10.yfrog.com/img10/3641/sepp5.gif
        6: http://img97.yfrog.com/img97/1118/sepp6.gif
        7: http://img69.yfrog.com/img69/2358/sepp7.gif
        8: http://img46.yfrog.com/img46/5748/sepp8.gif


        the upper cloud usually consists of pairs with one
        component Eurasian, the other North-American

        index-like evolution is seen, when on these pictures the
        clouds approach the y-axis high above the center=origin=(0,0)


        best example is:
        A/mallard/ALB/161/1977(H4N6)
        A/mallard/Ohio/83/1986(H4N6)
        they have 103 nucleotide-differences in HA but only one amino-acid is different.

        differences between these two in the 8 segments in promille:
        Code:
        segment:      1   2   3   4   5   6   7   8
        ------------------------------------------
        nucleotides: 53, 48, 16, 60, 44, 39, 34,287
        amino acids:  5,  2,  4,  1,  2, 17,  2,257
        I'm interested in expert panflu damage estimates
        my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

        Comment


        • #5
          Re: antigenic avian influenza evolution is mainly restricted

          update 22.Jan.2012

          full sequences examined


          Code:
          
          Dec.2009:
             1    2    3    41   43   5    61   68   7    81   82       segment
          --------------------------------------------------------------------------------
          3119,3118,2913,0111,0000,2897,1912,0706,2727,2632,0674    sequences examined
          0009,0062,0002,0000,0000,0016,0001,0000,0000,0377,0146    sequences with 0 amino-acid differences to the bird-index
          0100,0225,0008,0006,0000,0138,0004,0000,0000,0441,0225 sequences with 1 amino-acid difference to the bird-index
          
          
          Jan.2012:
             1    2    3    41   43   5    61   68   7    81   82       segment
          --------------------------------------------------------------------------------
          5972,6150,6132,0262,0914,5940,2814,0772,7419,5735,1574 sequences examined
          0024,0112,0002,0000,0031,0058,0000,0005,1167,0329,0104   sequences with 0 amino-acid differences to the bird-index
          0291,0489,0023,0000,0033,0422,0000,0005,1173,0558,0228   sequences with 1 amino-acid difference to the bitd-index

          more sequences available now and also looking at single segments,
          not just genomes
          I'm interested in expert panflu damage estimates
          my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

          Comment


          • #6
            Re: antigenic avian influenza evolution is mainly restricted

            the most restricted avian amino-acid evolution in the inner segments (HA,NA)
            is seen in H3-HA, see cloud picture above.

            Here is a mutation picture, sorted horizontally (positions) and vertically(viruses).
            Nukleotide mutations and amino-acid mutations.
            You can see how big variability (black areas) in the left nucleotide-part
            is met with only moderate variability in the right amino-acid part.
            Attached Files
            I'm interested in expert panflu damage estimates
            my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

            Comment


            • #7
              Re: antigenic avian influenza evolution is mainly restricted

              flu in mallards,teals is usually closest to the index and don't
              evolve away from it over the years as in chickens

              Some species which are also close to the index like
              shovelers,pintails,shorebirds almost exclusively occur
              in America, so we don't know how they react on H5N1
              which is the main strain in Asia.

              Then we often just have "ducks" in Asia, while America
              has mallards, teals. I wonder how these ducks are maybe
              (genetically) different from mallards or whether it's the
              behaviour (e.g. grazing in Rice-fields) or the changed
              pathogenicity of H5N1 that makes them accumulate
              amino-acid mutations or at least makes them catch
              such high amino-acid mutation segments.


              below some pictures of amino-acid mutation counts
              depending on sampled species and segments:

              does this look conform with the theory that waterborne flu (dabbling ducks)
              stays close to the index while only respiratory flu (fowl,geese,swan,gull,stint,
              some ducks) evolves away from the index ?

              The chickens usually won't catch the waterborne/index/dabbling flu,
              they need intermediate species, presumably non-dabbling ducks.

              (exception: Netherlands,H7N7,2003, windspead)



              ----------------------------------------------

              (last 4 letters of species name,
              horizontal: number of amino-acid differences from the consensus (0,1,..,30)
              vertical: count of samples with that difference
              file name : segment (e.g. ibis63.gif : segment 6, N3)
              the inner segments 4 and 6 (and partially 3 also) behave differently)



              mallard
              chicken
              duck
              turnstone
              pintail
              shorebird
              turkey
              shoveler
              gull
              goose
              quail
              avian
              pigeon,widgeon
              guinea fowl,fowl
              swan
              stork
              gadwall
              sanderling,starling
              knot,red knot
              cygnus olor (swan)
              pheasant
              stint
              bufflehead,redhead
              Attached Files
              I'm interested in expert panflu damage estimates
              my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

              Comment


              • #8
                2015 update:
                http://magictour.free.fr/BITSEPD0.GIF
                http://magictour.free.fr/disgr1.GIF
                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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