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Paradigm Shift Intervention Monitoring
The USDA recently released
six sets of sequences (HA, NA, MP) from swine in Costa Rica. As
noted previously, the HA
sequences had a large number of synonymous and non-synomous changes,
including receptor binding domain changes. However, phylogenetic
analysis provided compelling evidence support rapid evolution via
homologous recombination between isolates co-circulating in the swine
herd. This evolution was most dramatic in isolate A/swine/Costa
Rica/000125-3/2010. The HA sequence had a large number of
synonymous changes present in all six sequences (G291A, A453T, A708G,
G754A, T1023C, A1165A). Similarly, all six sequences had a large
series of non-synonymous – A142G (N34D), A212G (K57R), G408T (K122N),
G805A (E238K), A899G (K286R), C995T (A318V), C1140T (I375V) which
define a rapidly evolving sub-clade that had spread by clonal
However, these isolates had a number of additional changes shared by a subset of these sequences.
As noted previously, A/swine/Costa Rica/000125-3/2010, has two of the receptor binding domain changes, C592G (H184D) and G610T (D190Y), shared with A/swine/Costa Rica/000125-15/2010, which could be explained by further clonal expansion. However, additional changes which were shared with other isolates from the herd preclude this explanation for this additional evolution. A/swine/Costa Rica/000125-3/2010 shares two other polymorphisms, C528T (P162L) and A1227T, with A/swine/Costa Rica/000125-16/2010. Moreover, another polymorphism, A1222G (T394A) is shared with A/swine/Costa Rica/000125-19/2010, while G1357A (D439N) is shared with A/swine/Costa Rica/000125-20/2010. Thus, four of the five isolates have one or two polymorphisms exclusively shared with A/swine/Costa Rica/000125-3/2010, generating significant discordance. However, discordant combinations are note solely linked to A/swine/Costa Rica/000125-3/2010 polymorphisms. Another change, C647T, is shared by three other isolates, A/swine/Costa Rica/000125-14/2010, A/swine/Costa Rica/000125-16/2010, and A/swine/Costa Rica/000125-19/2010). Thus, all six isolates have polymorphism shared by a small subset (1 or 2) of the other isolates signaling significant recombination between isolates from this herd.
In additional to the recombination in the HA sequences, the NA and MP sequences also had evidence for recombination and discordance. The NA sequence also had multiple synonymous and non-synonymous polymorphisms that were found in all six sequences. However, two additional polymorphisms were present in two different subsets, which also involved A/swine/Costa Rica/000125-3/2010. C531T is shared with A/swine/Costa Rica/000125-19/2010, while C693T (A231V) is shared with A/swine/Costa Rica/000125-14/2010 and A/swine/Costa Rica/000125-16/2010. Moreover, the MP sequence has another polymorphism, C7T, that is not in A/swine/Costa Rica/000125-3/2010, but is shared by a different combination of isolates from the herd (A/swine/Costa Rica/000125-14/2010, A/swine/Costa Rica/000125-19/2010, and A/swine/Costa Rica/000125-20/2010).
Thus, the sequences from this herd clearly demonstrate rapid evolution via recombination, leading a novel sequences in each isolate and in multiple gene segments.
Although the isolates were from swine, these were pH1n1 sequences that jumped from human to swine and such sequences can easily jump back into humans. As noted previously, one of the shared receptor binding changes, D190Y, has already been detected in two human isolates, including a fatal case, A/England/4500186/2010, while another S188R is the position associated with dominance of the S188T sub-clade.
Thus, the recombination between herd members can generate new gen sequences that can seriously impact the human flu gene pool, and such changes to continue to be cause for concern.