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Paradigm Shift Intervention Monitoring
Beijing Institute of
Microbiology and Epidemiology has released a series of sequences at
Genbank from November, 2010 isolates, including five full or partial HA
sequences, Each of the three full sequences, A/Beijing/3872/2010,
had S188T. Although the two partial sequences, A/Beijing/3848/2010
did not cover the region encoding S188T, the vast majority of S188T
sub-clade sequences also have T1056C, G1171A (E377K), and G1403A
(S454N) and both partial sequences had all three markers.
Moreover, the three full sequences had additional markers in this
region, C1437T and C1656T which have also been seen in additional S188T
sequences and both partial sequences had these two markers also,
indicating all five HA sequences were from the S188T sub-clade which
had clonally expanded in Beijing in November, 2010. The dominance
of this sub-clade in late 2010 / early 2011 was widespread
throughout they northern hemisphere as well as in off-season isolates
from the southern hemisphere collected in this time frame.
However, one of the five sequences described above, A/Beijing/3872/2010, was missing two consecutive markers, T1056C and G1171A which are found in virtually all S188T sub-clades. This isolate had also gained two markers, C897A and A1215G located in the same region. These two markers were present in other pH1N1 sequences (see list here and here), including A/Beijing/22811/2009, which has C897A and was wild type at positions 1056 and 1171.
Moreover, A/Beijing/3872/2010 has the upstream markers, T72C, C144T, G366A, A478G (S146G), G605C (S188T), G640A (A200T). which are present in the other two November sequences. Thus, Bejing/3872 has the nine common markers flanking the short region (between positions 897 and 1215), were there are four changes (the loss of T1056C and G1171A coupled with the gain of C897A and A1215G).
These concentrated changes are most easily explained by homologous recombination because three of the four changes are present on an earlier Beijing sequence and the rare fourth change is present on two H1N1 sequences which are also wild type at positions 1056 and 1171 and therefore each also has three of the four changes (and the small size of the Beijing sequence database suggests that a sequence with all four changes already exists) could be acquired via a single recombination event producing the acquisition between positions 897 and 1215.
Thus, the five Beijing sequence represent clonal expansion of an evolved S188T sub-type, and A/Beijing/3872/2010 is an example of additional rapid evolution via homologous recombination.