low mutation rates in flu-viruses

[gsgs]

I looked at 3 groups of viruses:

"2004": 11 H5N1- viruses from Henan,2004
"1997": 6 H5N1 - viruses from Hubei,1997
"1977": 19 avian viruses from Hongkong, 1975-1979


the minimum distance between the groups in the 8 segements is:

1977-1997: 346,119,183,735,146,1069,097,123
1997-2004: 100,030,079,191,033,0143,038,089
1977-2004: 290,114,167,810,133,1080,136,191

(distance=1/100 % of nucleotides changed)

This is very low.
to compare: the average distance of a Qinghai-virus to the
original Qinghai-strain from Febr.2005 is 030 per year !

that would make 600 for 1977-1997, 210 for 1997-2004, 810 for 1977-2004

For 1968 H3N2 the rate was also about 030 for the first 5 years,
but then it went down to ~020. I assume in new reassorted viruses
the mutation rate is higher because more mutations survive
when the sequences are not yet very optimal.

human H3N2, 1968(1972)-1998:492,594,510,1284,543,828,363,534

There are also some examples for preserved sequences in swine.
I'm not aware of such examples of low mutation rates
in human influenza except the "freeze" 1957-1977 in H1N1,
lab-escapes or vaccine strains.

schina

[cartski]

Re: low mutation rates in flu-viruses

I'm sorry, but I need much more rudimentary statements about what the science is in order to follow your experiment.

What's the original thread about this? Statements from Vallat about the "stability" of the H5N1 virus?

And you're saying that the rate of genetic change in the Quingai virus is very low, and therefore supports Vallat's statements?

J.

[gsgs]

Re: low mutation rates in flu-viruses

no, it's not directly related to Vallat's statement.
More because of our ongoing discussion since 2006
about some strange flu-sequences ("Canadian Swine", and others)
which were preserved since many years,
even decades, while usually flu mutates with about 30 nucleotide-
changes per year.


list here:

http://www.setbb.com/fluwiki2/viewtopic.php?t=187&mforum=fluwiki2

well, the "original thread" is maybe this:

http://67.210.96.104/forum/showthread.php?t=51782

where they mentined the preservation in Africanstarling
and that this is unexplained.

[Extrapolation]

Re: low mutation rates in flu-viruses

Kindly put, and in civil, factual metaphor:

I believe, it is (although masked well) the ongoing one-sided "debate" between gsgs and Dr. Niman's point of view in re: recombinetics.

Sort of an earth is flat postulation, and a weak defense thereto.

But point counterpoint is all it is. A tit for tat.

[gsgs]

Re: low mutation rates in flu-viruses

it's not really about recombination (IMO)

recombination-theory can't explain this either.
I had speculated that vaccine strains might have become wild
or frozen viruses might have escaped from a lab.

But this example speaks against this:
we have two etappes of low mutation:
1977-1997 and 1997-2004

I think, we should be looking for viruses hiding in the bodies
for weeks or months without replicating.
Or abiotic reservoirs for some species, viruses surviving in water
or such. This is still rare, but it does happen.
Maybe one special species or special environment,
I don't know.

[Extrapolation]

Re: low mutation rates in flu-viruses

I stand corrected.

[X-fingers]

Re: low mutation rates in flu-viruses

it's not really about recombination (IMO)

recombination-theory can't explain this either.
I had speculated that vaccine strains might have become wild
or frozen viruses might have escaped from a lab.

But this example speaks against this:
we have two etappes of low mutation:
1977-1997 and 1997-2004

I think, we should be looking for viruses hiding in the bodies
for weeks or months without replicating.
Or abiotic reservoirs for some species, viruses surviving in water
or such. This is still rare, but it does happen.
Maybe one special species or special environment,
I don't know.

Or possibly expand the data-set beyond these 36 viri? Why are they representative?

The 1977 group consists of what type of virus?

The two etappes of low mutation are just your data points aren't they?

And question your method too - the 30 Nt change rate isn't a universal law by far and change rates differ over reservoirs.

*

And how would 'hiding viruses' or 'water viruses' outcompete their cousins who are replicating all the time? Or they don't and that's why you work with only the 36 examples?

Numquam ponenda est pluralitas sine necessitate

[gsgs]

Re: low mutation rates in flu-viruses

I can post more data, if there is interest...

those 3 groups were chosen, because they were apparant, when looking
at the list of all suspected preservations.

see here:

http://www.setbb.com/fluwiki2/viewtopic.php?t=187&mforum=fluwiki2

I did a systematic computer-search for low-mutations per year using all
genbank and lanl flu-sequences until Mar.2007

those 1977,1997,2004 is probably the most obvious low-mutation group for H5N1 and ancestor segments
which you will find at genbank. Another preservation : HK/97-Vietnam/05

the 30NT change is observed almost everywhere in flu.
I made graphics to demonstrate this for all segments, probably posted
also at flutrackers earlier. (24.Jul-2.Aug 2007) I will search, if you are interested.
edit: found this: http://67.210.96.104/forum/showpost.php?p=94397
(for PB2 - but I did the same for other segments)

it is assumed and seems reasonable that the mutations happen during replication.
So abiotic viruses surviving some time without replication should have fewer mutations.
(discarding recombinations,reassortments)



I took all available viruses
Hubei 1997,H5N1
Henan 2004,H5N1
Hongkong,avian 1970-1979
where (almost) full genomes were available.
I didn't find similar interesting viruses/groups from HK or China >1980,1990
with chances for low-mutation rates
when just looking at my list, but didn't (yet) search systematically.

here is the list of the 36:

>A/Sw/Henan/wy/04(H5N1)
>A/TSp/Henan/1/04(H5N1)
>A/TSp/Henan/2/04(H5N1)
>A/TSp/Henan/3/04(H5N1)
>A/TSp/Henan/4/04(H5N1)
>A/Ck/Henan/01/04(H5N1)
>A/Ck/Henan/12/04(H5N1)
>A/Ck/Henan/13/04(H5N1)
>A/Ck/Henan/16/04(H5N1)
>A/Ck/Henan/210/04(H5N1)
>A/Ck/Henan/wu/04(H5N1)

>A/Ck/Hubei/wh/97(H5N1)
>A/Ck/Hubei/wi/97(H5N1)
>A/Ck/Hubei/wj/97(H5N1)
>A/Ck/Hubei/wk/97(H5N1)
>A/Ck/Hubei/wl/97(H5N1)
>A/Ck/Hubei/wm/97(H5N1)

>A/Dk/HK/7/1975(H3N2)
>A/Dk/HK/23/1976(H5N3)
>A/Dk/HK/24/1976(H4N2)
>A/Dk/HK/d73/1976(H6N1)
>A/Ck/HK/17/1977(H6N1)
>A/Dk/HK/147/1977(H9N6)
>A/Dk/HK/205/1977(H5N3)
>A/Dk/HK/d134/1977(H6N2)
>A/Gs/HK/23/1978(H5N3)
>A/Gs/HK/23/1978(H5N3)
>A/Dk/HK/278/1978(H2N9)
>A/Dk/HK/312/1978(H5N3)
>A/Dk/HK/319/1978(H2N2)
>A/Dk/HK/342/1978(H5N2)
>A/Dk/HK/342/1978(H5N2)
>A/Dk/HK/365/1978(H4N6)
>A/Dk/HK/394/1978(H5N3)
>A/Dk/HK/562/1979(H10N9)
>A/Dk/HK/784/1979(H9N2)

[Vibrant62]

Re: low mutation rates in flu-viruses

There is another theory that could explain the phenomenom.

We know that viri held in deep freeze in artic and antarctic ice are still - sometimes - viable when released from deep freeze.

It is entirely possible that birds or other vectors have transported viruses to areas where subzero temperatures predominate, and that, with global warming and ice melts such viruses are released again into the environment.

Thus a virus from 1978 (or prior) could have become locked in ice, and then become released as warming has resulted in ice melts with a subsequent exposure to a viable host, restarting the cycle.

To test such a theory, where exactly were viral samples that matched earlier (unchanged) samples identified? Was it in a cold temperature area? Could it explain what has been seen in genetic sequence samples?

Just to add to the mix...

[gsgs]

Re: low mutation rates in flu-viruses

not much ice in Hongkong,Hubei,Henan.

Also, the low mutation was 1977-1997 as well as 1997-2004,
and in several segments so it would have to involve multiple
freezing events and reassortments.
Another H5N1-low-mutation-example was
HK/1997-Vietnam/2005.

No such low mutation rates are found in the Qinghai strain
(except the Hungary-Suffolk virus)
which is at home in the west Sibirian wetlands with first freezing
as early as July in the nothern areas.

[X-fingers]

Re: low mutation rates in flu-viruses

I looked at 3 groups of viruses:

"2004": 11 H5N1- viruses from Henan,2004
"1997": 6 H5N1 - viruses from Hubei,1997
"1977": 19 avian viruses from Hongkong, 1975-1979


the minimum distance between the groups in the 8 segements is:

1977-1997: 346,119,183,735,146,1069,097,123
1997-2004: 100,030,079,191,033,0143,038,089
1977-2004: 290,114,167,810,133,1080,136,191

(distance=1/100 % of nucleotides changed)

This is very low.

Wouldn't it be helpful to include the segment names wih the table?

1977-1997: 346,119,183,735 (Na?),146,1069 (Ha?) ,097,123

[gsgs]

Re: low mutation rates in flu-viruses

usual enumeration : (1,2,3,4,5,6,7,8) = (PB2,PB1,PA,HA,NP,NA,M,NS)

I should add, that these low rates are often only in one or few segments
and only in one or few members from the groups, while the others
have more mutations. Want the whole table ?

OK, I uploaded it here:

http://magictour.free.fr/panflu/schina.l1

numbers are differences in 1/100 percent for the 8 segments, 44 viruses

[gsgs]

Re: low mutation rates in flu-viruses

stasis
Taubenberger et.al 2002 refer to :
Webster, R. G., G. B. Sharp, and E. C. Claas. 1995. Interspecies transmission of influenza viruses. Am. J. Respir. Crit. Care Med. 152:S25-30.

http://cat.inist.fr/?aModele=a...
> In contrast to the rapid, progressive changes in both the
> nucleotide and amino acid sequences of
> mammalian virus gene lineages, avian virus genes show far less
> variation and, in most cases, appear to be in evolutionary stasis

is this true ? I can't verify this. It's not, what we see with H5N1.
(nor H9N2,H7N?,...)

[gsgs]

Re: low mutation rates in flu-viruses

I assume human flu evolves with about 35 nucleotide-changes
per year per genome and avian flu with about 45.

After many years, some mutations will undo previous mutations
instead of forming new ones, so the distance between
2 strains grows more slowly and after about 200 years
remains almost constant.



total differences for the 8 segments:
9 >A/Brevig Mission/1/1918(H1N1)
----------------------------------------------
1:313,357,282,784,178,678, 68,239, 1949(H10N7)
2:318,372,269,818,191,688, 72, 38, 1927(H7N7)
3:317, 0,263,522,193, 0, 68, 37, 1902(H7N7) [I don't trust this sequence, maybe incorrect]
4:330,344,279,792,179,567, 68, 54, 1963(H3N8)
5:321,358,273,572,189,164, 72, 49, 1959(H5N1)
6:358,353,291,574,207,241, 95, 73, 2006(H5N1)
7:349,361,300,589,204,235, 93, 73, 2005(H5N1)
8:101,105,110,112, 66, 72, 39, 38, 1931(H1N1)
9: 0, 0, 0, 0, 0, 0, 0, 0, 1918(H1N1)
10:115, 87, 97,141, 74, 96, 40, 33, 1935(H1N1)
11:140,118,125,178, 86,112, 37, 36, 1940(H1N1)
12:240,211,196,262,133,196, 73, 75, 2007(H1N1)
13:167,359,136,583,113,707, 45, 48, 1957(H2N2)
14:222,365,174,803,133,696, 59, 69, 1972(H3N2)
15:270,403,239,806,188,691, 81, 95, 2007(H3N2)


differences in 1/10 percent:

9 >A/Brevig Mission/1/1918(H1N1)
1:137,156,131,477,118,489, 69,284,
2:139,163,125,494,127,496, 73, 45,
3:138, 0,122,549,128, 0, 69, 44,
4:144,151,129,475,119,410, 69, 64,
5:140,157,126,338,126,116, 73, 58,
6:156,155,135,339,138,178, 96, 88,
7:153,158,139,350,136,173, 94, 88,
8: 44, 46, 51, 65, 44, 51, 39, 45,
9: 0, 0, 0, 0, 0, 0, 0, 0,
10: 50, 38, 45, 82, 49, 70, 40, 39,
11: 61, 51, 58,104, 57, 79, 37, 42,
12:105, 92, 91,154, 88,138, 74, 89,
13: 73,157, 63,345, 75,511, 45, 57,
14: 97,160, 80,481, 88,503, 60, 82,
15:118,177,111,483,125,499, 82,113,



12:240,211,196,262,133,196, 73, 75, 2007(H1N1)
1386 changes in 89 years (~25 of these inactive) = 22 mutations per year

11:140,118,125,178, 86,112, 37, 36, 1940(H1N1)
832 differences in 22 years = 38 mutations per year

10:115, 87, 97,141, 74, 96, 40, 33, 1935(H1N1)
683 differences in 17 years = 40 mutations per year

14 >A/Russia/WO0200884/72(H3N2) - 15 >A/Texas/UR06-0356/2007(H3N2)
122,150,121,196, 98,130, 41, 45

903 differences in 35 years = 26 mutations per year




Qinghai H5N1 got its PB2 almost directly from A/Ck/Scotland/1959(H5N1).
Also probably M,NS and maybe HA,NP,NA :
73,117,111,131, 89,129, 64, 67 differences in 0/00 , 46 years

while PB1 is from 1957 panflu and PA from the 1963 Ukraine duck. Or similar/related viruses.

[HenryN]

Re: low mutation rates in flu-viruses

I'm sorry, but I need much more rudimentary statements about what the science is in order to follow your experiment.

What's the original thread about this? Statements from Vallat about the "stability" of the H5N1 virus?

And you're saying that the rate of genetic change in the Quingai virus is very low, and therefore supports Vallat's statements?

J.

Vallat said nothing about "mutation" rates.