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Commentary
Widespread High
Frequencies of H1N1 D225E In Italy
Recombinomics
Commentary 14:41
February 01, 2010
In contrast, samples from Pavia and Milano, collected between July and November had high frequencies of D225E throughout the collection period, with D225E in 45 of the 77 HA sequences. Thus, 58 out of 103 HA sequences had D225E and none had D225G or D225N, demonstrating a clustering in time and space for D225E.
Moreover, the D225E was found in multiple sub-clades. In Pavia 11 of the 13 sequences with D225E also had C940T, a polymorphism associated with D225E isolates. In contrast C940T was only found in 10 of the D225E sequences from Pavia and Milan, even though the HA genetic region was covered in the vast majority of the 45 D225E isolates (see list here).
This concentration of D225E sequences is not limited to Italy. D225E is also common in Spain (where C940T is rarely found). In addition, recently released sequences collected in July and August in the UK also have a high frequency of D225E, and a much lower frequency of D225G/N.
These frequencies are in sharp contrast to Ukraine, where D225G and D225N are common in tissues collected from fatal cases. Moreover, none of the sequences from Ukraine have D225E. Thus, this clustering of position 225 polymorphisms in time and space contradicts the WHO working hypothesis that D225G/N polymorphisms are spontaneous and sporadic and are due to copy errors.
The clustering, and requirement for multiple independent introductions over a short time period, are much more easily explained by homologous recombination than random mutation, as was seen in the fixing of H274Y in seasonal H1N1, and is being repeated for pandemic H1N1.
These data support homologous recombination as the driving force between these rapid changes and movement of position 225 polymorphisms from one pandemic H1N1 sub-clade to another, and strongly discount the role of copy errors in rapid influenza evolution.
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