Rhiza Labs FluTracker Forum

here an example of two viruses with an excess of synonymous differences
in 6 segments and an excess of non-synonymous ones in NA


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

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,  2,108,  2,257
.

.


differences in segment 6 at codon-position :

1:46
2:5
3(usually synonymous):6


------------edit----------------------
sorry, forget this. I had an alignment error in segment 6

_________________
no patents on genes, publish the GISAID sequences !

we have quite some recent new avian genomes from USA at genbank,
but most from 2002-2008, nothing from <1980,
no new good relative of 1918-flu.


Below are selected North American avian amino-acid sequences ,
segments 1,2,3,5,7,8 close to the bird index over long time spans

as you can see it doesn't accumulate protein differences in these even over 30 years ! (but not so in segments 4,6)
But usually, when it goes into chickens or gulls or mammals
then it starts to mutate away !
Evidence is growing that in mallards it usually transmits
waterborne.


first column: difference in promille,
second column: number of protein-differences
3rd column : number of amino-acids considered


1
0 0 760 15 >A/turkey/CO/118899/1972(H5N2),1972//
0 0 760 30 >A/mallard Dk/ALB/57/1976(H5N2),1976/08/12
0 0 760 111 >A/Gs/MN/5733-1/1980(H9N2),1980/01/01
0 0 760 272 >A/mallard/Ohio/424/1988(H3N2),1988//
0 0 760 806 >A/blue-winged teal/Texas/82/01(H2N1),2001//
0 0 760 1131 >A/green-winged teal/Ohio/1292/05(H4N6),2005//
0 0 756 2138 >A/blue-winged teal/Minnesota/Sg-00450/08(H4N8),2008/08/20

2
0 0 758 41 >A/mallard Dk/ALB/224/1977(H7N5),1977/08/05
0 0 758 123 >A/mallard Dk/ALB/645/1980(H5N2),1980/08/22
0 0 758 202 >A/mallard Dk/ALB/438/1985(H3N4),1985/08/20
0 0 758 355 >A/mallard/Alberta/11/1991(H9N2),1991/08/09
0 0 758 449 >A/turkey/Utah/24721-10/1995(H7N3),1995//
0 0 758 644 >A/mallard/Minnesota/192/99(H4N6),1999//
0 0 758 1110 >A/mallard/Alberta/154/03(H6N5),2003/08/03
0 0 758 2002 >A/American wigeon/Minnesota/Sg-00231/07(H4N6),2007/09/29

3*
0 0 717 501 >A/mallard/ALB/196/96(H10N7),1996/08/
0 0 717 696 >A/mallard/Minnesota/410/00(H5N2),2000//
0 0 717 1130 >A/ruddy turnstone/New Jersey/26/04(H10N7),2004//
0 0 717 2182 >A/mallard/Minnesota/Sg-00672/08(H3N8),2008/08/03
13 1 717 45 >A/canvasback Dk/ALB/274/1977(H4N6),1977/08/09
13 1 717 175 >A/mallard Dk/Tennessee/11464/1985(H1N1),1985/01/16
13 1 717 329 >A/blue-winged teal/ALB/136/1990(H4N3),1990/08/22
13 1 717 555 >A/mallard/Minnesota/95/98(H4N2),1998//

3
13 1 717 43 >A/mallard Dk/ALB/46/1977(H1N1),1977/08/08
13 1 717 90 >A/mallard Dk/ALB/106/1979(H4N2),1979/08/07
27 2 715 234 >A/green-winged teal/Ohio/466/1987(H3N8),1987//
27 2 716 12 >A/turkey/Oregon/1971(H7N3),1971//
27 2 717 39 >A/mallard Dk/ALB/42/1977(H1N6),1977/08/02
27 2 717 156 >A/redhead Dk/ALB/357/1983(H11N9),1983/08/07
27 2 717 246 >A/green-winged teal/Louisiana/213GW/1987(H1N1),1987//
27 2 717 329 >A/blue-winged teal/ALB/136/1990(H4N3),1990/08/22
27 2 717 376 >A/pintail/Alberta/129/1993(H10N7),1993/12/01
27 2 717 919 >A/ruddy turnstone/Delaware/262/02(H2N1),2002//
27 2 717 1587 >A/glaucous gull/Alaska/44199-097/06(H13N3),2006/09/25
27 2 717 1809 >A/N.shoveler/Alaska/7MP0954/07(H4N6),2007/09/06

5
0 0 499 7 >A/turkey/Canada/1963(H6N8),1963//
20 1 485 1429 >A/N.pintail/Alaska/44160-060/06(H12N5),2006/08/18
20 1 494 258 >A/mottled Dk/LA/32M/87(H6N2),1987//
20 1 495 548 >A/mallard/MN/284/98(H7N3),1998//
20 1 499 17 >A/Dk/Pennsylvania/1/1969(H6N1),1969//
20 1 499 23 >A/Dk/Memphis/928/1974(H3N8),1974//
20 1 499 71 >A/pintail Dk/ALB/303/1977(H10N7),1977/09/03
20 1 499 108 >A/pintail Dk/ALB/462/1979(H3N6),1979/08/10
20 1 499 164 >A/Dk/Washington/4954/1983(H3N8),1983//
20 1 499 267 >A/Dk/Louisiana/188D/1987(H12N5),1987//
20 1 499 382 >A/mallard/ALB/199/1992(H6N5),1992/12/01
20 1 499 483 >A/mallard/ALB/201/96(H2N3),1996/08/
20 1 499 671 >A/red knot/Delaware/1269/00(H10N7),2000//
20 1 499 1020 >A/blue-winged teal/Ohio/658/04(H7N3),2004//
20 1 499 1748 >A/N.shoveler/CA/HKWF1325/07(H8N4),2007/12/09

7
0 0 317 2096 >A/mallard/Minnesota/Sg-00170/07(H6N1),2007/09/16
0 0 322 724 >A/herring gull/Delaware/281/98(H5N8),1998//
0 0 323 549 >A/Dk/Pennsylvania/Sg-00269/1995(H2N3),1995//
0 0 324 725 >A/shorebird/Delaware/27/98(H5N8),1998//
0 0 339 314 >A/red knot/Delaware/2561/87(H10N5),1987//
0 0 344 640 >A/mallard/Alberta/226/98(H2N3),1998//
0 0 348 12 >A/Turkey/CA/189/66(H9N2),1966//
0 0 348 457 >A/Qa/Arkansas/29209-1/93(H9N2),1993//
0 0 348 1257 >A/mallard/Ohio/671/02(H4N6),2002/08/19
0 0 349 351 >A/mallard/Ohio/298/1987(H4N6),1987/10/19
0 0 350 159 >A/domestic Dk/MN/1086/1980(H4N8),1980/09/29
0 0 350 197 >A/pintail Dk/NY/155/1982(H4N3),1982/12/01
0 0 350 357 >A/mallard/Alberta/321/88(H9N2),1988//
0 0 351 4 >A/turkey/Canada/1963(H6N8),1963//
0 0 351 16 >A/Turkey/Oregon/71(H7N3NSB),1971//
0 0 351 24 >A/blue Gs/WI/711/1975(H5N2),1975//
0 0 351 26 >A/Canada Gs/Wisconsin/902/1975(H5N2),1975//
0 0 351 36 >A/mallard Dk/ALB/25/1976(H3N1),1976/08/11
0 0 351 178 >A/turkey/Minnesota/1598/1981(H5N2),1981/11/06

8
0 0 320 398 >A/mallard/Alberta/11/91(H9N2),1991//
0 0 331 666 >A/mallard/Alberta/111/99(H4N6),1999//
0 0 353 31 >A/mallard/Wisconsin/34/1975(H5N6),1975//
0 0 353 62 >A/mallard Dk/ALB/46/1977(H1N1),1977/08/08
0 0 353 126 >A/pintail Dk/ALB/599/1979(H4N2),1979/08/11
0 0 353 203 >A/mallard Dk/ALB/797/1983(H11N3),1983/08/23
0 0 353 292 >A/Dk/Ohio/421/87(H7N8NS1),1987//
0 0 353 529 >A/Ck/New Jersey/15906-9/96(H11N1),1996//
0 0 353 1176 >A/American black Dk/North Carolina/675-075/04(H3N2),2004//
0 0 353 1948 >A/green winged teal/CA/AKS1305/08(H11N9),2008/01/26

_________________
no patents on genes, publish the GISAID sequences !

A CDC EID PDF (more acronyms to follow, primarily HA and NA)

http://www.cdc.gov/eid/content/16/11/pdfs/10-0361.pdf

Reassortment of Ancient Neuraminidase and Recent Hemagglutinin in Pandemic (H1N1) 2009 Virus


Sequence analyses show that the outbreak of pandemic (H1N1) 2009 resulted from the spread of a recently derived hemagglutinin through a population of ancient and more diverse neuraminidase segments. This pattern implies reassortment and suggests that the novel form of hemagglutinin conferred a selective advantage.


To examine the effects of intersegment reassortment on sequence diversity, we analyzed the pattern of nucleotide substitutions in pandemic (H1N1) 2009 virus and compared it with that of other influenza A virus genotypes (see http://www.biol.sc.edu/~austin).

skipping to conclusion ......

The 9 aa residues in HA not found in our sample of pre-2009 influenza (H1N1), but fixed in our sample of pandemic (H1N1) 2009 virus, are candidates for selectively favored amino acid replacements in pandemic (H1N1) 2009 virus.

at the time of that analysis ~1500 avan flu genomes were
available at genbank.
Now we have 2524 ! I downloaded them, converting now ...
(this is all very tedious)

...

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

here is the new cloud from these 2518 (some removed because
of many mutations,misalignment or possible errors (or recombination ...))
for segment 1

compare with the old one:
http://img682.yfrog.com/img682/9668/sepp1.gif

_________________
no patents on genes, publish the GISAID sequences !

segment 2, 6529-93 sequences
(the 93 most distant sequences were removed)

_________________
no patents on genes, publish the GISAID sequences !

pages 12
viewtopic.php?f=26&t=1734&start=110

---------------------------------------------------
(vii) Comparison of 4-fd sites. We examined the numbers of changes at sites that are fourfold degenerate (4-fd). These sites can have any of the four bases, with no resulting amino acid replacement. Such sites have been shown to evolve nearly as rapidly as pseudogenes, the most rapidly evolving sequences in genomes. If influenza virus genes have been evolving in birds for long enough to reach evolutionary stasis (35), as is suggested by the high S/N ratios described above, one would predict that at [as] many of the sites where fourfold degeneracy is [as] possible [...] all four bases would be present in the avian clade unless the constraints of RNA secondary structure limit the accumulation of synonymous changes. By contrast, in the mammalian clade, if all subsequent mammalian influenza viruses acquired their NP gene segment from the 1918 virus (i.e., comparatively recently), most of the 4-fd sites would still have the same base. Indeed, of 211 4-fd sites shared by the 1918 strain and SwIowa30 (a closely related mammalian isolate), 85% have the identical base. By contrast, when the 1918 strain is compared with TyMN80 (a closely related avian isolate), of 212 shared 4-fd sites only 58% have the identical base. Among avian isolates, however, where one might expect to find greater heterogeneity at 4-fd sites, the percentages of shared sites are high. For example, 85% of the shared 4-fd sites are identical in a comparison between TyMN80 and DkMT53 (members of the North American avian clade). The number drops to 73% between TyMN80 and DkBav77 (a North American avian strain and a Eurasian avian strain). Since 4-fd sites are expected to become heterogeneous over time (two sequences should show about 25% identity at fourfold sites at equilibrium), these data suggest that nonrandom forces are acting on the avian strain sequences. These could involve periodic homogenization events both within and between avian clades or selection, as discussed above, if a number of 4-fd sites are involved in RNA secondary structure. Nevertheless, the low percentage of shared fourfold sites between sequences of the 1918 strain and avian strain sequences is another indication of substantial evolutionary distance and makes it less likely that the NP gene segment came directly from a currently known avian source just before the pandemic.
-----------------------------------------------------------------------
generate the % of equal nucleotides at the 4-fd sites
for all ~5M pairs in the list...

GC*,CG*,GG*,CT*,CC*,TC*,AC*,GT*
.

    A  C   G    T
---------------------
A| kn  T  RS  IM
C| qh  P  R    L
G| ed  A  G   V
T| }y  S  }Wc Lf
------------------------
.
.

_________________
no patents on genes, publish the GISAID sequences !