niman wrote:
Since the recombination in Beijing is so obvious and clear cut, it is worth going through the data and associated concepts in detail, so even the casual reader can understand. Beijing released 5 closely related sequences, and even though 2 of the 5 were only partials, they had the expected markers in the published portion, so it is clear that all five isolates represent an evolved version of the S188T-subclade, which has 11 HA changes.
Four of those changes define the sub-clade. They were in sequences first seen in the late spring and throughout the summer (in India, Thailand, Ghana, Australia, New Zealand, South Africa). Three of these four changes led to changes in the protein (S188T, E377K, and S454N) and all four changes are in virtually all sequences with S188T. Thus, these were "early" changes. The other 7 changes seen in Beijing followed, and most can be found in other sequences with S188T, with the best matches in recent sequences from Asia or Australia.
However, one of the Beijing sequences had four clustered changes, which included the loss of 2 of the 4 "early" markers. The two "new" markers were close to the "missing" old markers, creating a strong signal for recombination involving a relative short segment of the gene (the gene has 1701 positions, and the changes were from position 897 to 1215). Recombination was supported by an earlier Beijing sequence (from late 2009), which had 3 of the 4 changes (at positions 897, 1056, and 1171). The 4th change (at position 1215) was rare, but found in two earlier sequences which also had the wild type sequence at positions 1056 and 1171, so they also had 3 of the 4 changes (at positions 1056, 1171, and 1215) so it is likely that these earlier isolates recombined to produce one sequence with all four changes, which then recombined with the November, 2010 isolate in Beijing to produce the recombinant. Thus, expalining four clustered changes involving sequences already present in the H1N1 database is very straightforward, since 3 of the 4 were already circulating in a known Biejing H1N1 sequence.
In contrast, trying to explain these four clustered changes by "random mutation" is very difficult and lacks credibility.
I produced a simple picture displaying the discussed recombination markers.
The minus sign indicates that sequence is
wild type at the respective amino acid position.
Attachment:
Recombination_Example_1c.jpg
Dr Niman, please advise possible picture mistakes.
Beijing/3884 has A1002G (not C897A, as indicated in the table), which isn't relevant to the discussion. All isolates except for the recombinant, A/Beijing/3872/2010, have T1056C.
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