antigenic avian influenza evolution is mainly restricted

[gsgs]

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/showthread.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/showthread.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

 

[gsgs]

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

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

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

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

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

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

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

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

 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

 

[gsgs]

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

 

[gsgs]

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:

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

 

[gsgs]

Re: antigenic avian influenza evolution is mainly restricted

update 22.Jan.2012

full sequences examined

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

 

[gsgs]

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.

 

[gsgs]

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

 

[gsgs]

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