Genomic "variation" 17 September 2003
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Christopher J Noble,
postdoctoral fellow
Bern Switzerland

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Re: Genomic "variation"

I am glad that Alan F Miceli understands what the Perth group mean when they refer to genomic variation. The Perth Group have used this term to refer to several different things depending on the context.

"The type 3 Sabin poliovirus differed from its neurovirulent progenitor at only 10 nucleotide positions after 53 in vitro and 21 in vivo passages in monkey tissues. In 1977, H1N1 influenza A virus reappeared in the human population after 27 years of dormancy with sequences mainly identical to those of the 1950s virus."

Here despite their repeated protestations that "Neither are we interested in the genomic variation with time, that is, evolution of the genome, but the genomic variation at a given time" they are in fact specifically referring to the genomic variation of these viruses over time. More importantly, these examples are not, as the Perth Group would have you believe, representative of the normal evolution rate of these viruses. "Other viruses also demonstrate remarkable stability in some situations." In fact both poliovirus and influenza have high evolution rates. Influenza has an evolution rate of around 0.2% substitutions per site per year. The evolution rate of poliovirus has been estimated to be as high as 2% (1). There has been no explanation so far of why the Perth Group cited examples of "remarkable stability in some situations" rather than normal evolution rates.

When the Perth Group state "the genomes of the most variable RNA viruses do not differ by more than 1%" they are referring to a study by Cattaneo et al (2) looking at the variation in the genome of measles isolates from one patient. This is not representative of the interhost variation of measles or of RNA viruses in general.

When the Perth Group refer to the variation in HIV sequences "How then does Brian Foley explain that differences of up to 40% as is the case in the "HIV" sequences (10) (11) represent the genome of one and the same object?". They refer firstly to a paper by Gurtler et al (3) describing a divergent HIV subtype representing the largest divergence across all HIV-1 viruses.

Notice that in the case of measles they refer to the variation in one patient and in the cases of poliovirus and influenza they are obviously only referring to poliovirus type and one influenza A type. Yet in HIV they refer to the variation between all HIV-1 virus types and subtypes.

The Perth Group argue that the paper by Kozal et al (4) shows that isolates of HIV-1 M group subtype B vary by up to 40% from each other. "It is true that a difference of up to 40% exists between HIV-1 M group subtype B and HIV-1 O group and HIV-1 group N but also within the HIV-1 M group." In fact the paper does not say this at all. The Perth Group are confusing the percentage genetic variation between a pair of sequences and the percentage of amino acid sites that are seen to vary in a large number of sequences. The two are fundamentally different.

The arguments used by the Perth Group are deceptive. At different time they refer to either genetic variation over time or that at a given time, variation between virus types or variation within virus types, variation within a single host or variation across large populations.

Any of their arguments as to why the genome sequences of HIV are implausible can also be applied to other viruses such as polio or influenza.

Again many of the references cited by the Perth Group do not support their claims. It is important if you want to understand the arguments regarding the existence of HIV to read the papers. Do not rely on the Perth Groups characterisation of what a paper says. Do not rely on selective quotations.

Be skeptical.

(1) Kew OM, Sutter RW, Nottay BK, McDonough MJ, Prevots DR, Quick L, and Pallansch MA, Journal of Clinical Microbiology, 36, 1998, 2893-2899.

(2) 3. Cattaneo R, Schmid A, Rebmann G, Baczko K, Ter Meulen V, Bellini WJ, Rozenblatt S, Billeter MA. Virology. 1986 Oct 15;154(1):97-107.

(3) Gurtler LG, Hauser PH, Eberle J, von Brunn A, Knapp S, Zekeng L, Tsague JM, Kaptue L. A new subtype of human immunodeficiency virus type 1 (MVP-5180) from Cameroon. (1994) J Virol 68:1581-1585

(4) Kozal MJ, Shah N, Shen N, Yang R, Fucini R, Merigan TC, Richman DD, Morris D, Hubbell E, Chee M, Gingeras TR. (1996). Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays. Nat Med 2:753-759.

Competing interests:   None declared