Aggregation H5N1 Single Nucleotide Polymorphisms Confirmed
Recombinomics Commentary 11:40
January 15, 2008
Sequences of twelve 2007 chicken isolates from Nigeria were just made public at Genbank. These sequences fully support the aggregation of single nucleotide polymorphisms previously described in the human influenza HA sequence, A/Nigeria/6/07. Four of the chicken isolates were virtually identical to the human influenza HA sequence (see list below), while six more were closely related. Two of the isolates were closely related to a subset of 2006 isolates from Nigeria.
The “Aggregation” paper described 14 polymorphisms that were shared with other clade 2.2 isolates. All 14 of these polymorphisms were present in the newly released chicken influenza sequences from Nigeria (see list here). Thirteen of the fourteen were in the four sequences virtually identical to the human influenza sequence. The only polymorphism, C1480T, not in the four closely related sequences was present in the two isolates related to the subset of 2006 isolates. In addition, seven of the fourteen polymorphisms (G295A, A433G, G643A, G781A, C981T, G1685A, A1708G) were present in the ten most closely related sequences.
These data support the previously described aggregation of single nucleotide polymorphisms from diverse clade 2.2 sub-clades.
This aggregation is most easily explained by homologous recombination in H5N1 influenza A. These data seriously challenge the current dogma of influenza evolution which postulates genetic drift through selection of errors generated during replication. The presence of the newly acquired sequences in related clade 2.2 sequences does not support generation of these sequences by de novo errors. Moreover, the presence of the same series of changes in multiple sequences from two species indicates these data are not due to lab error or artifact.
Instead, the polymorphisms are acquired via homologous recombination in co-infected hosts. The tracing of these polymorphisms allows for the identification of polymorphism distribution routes and predictions of polymorphism acquisitions linked to expected co-infections.
This mechanism is further supported by the concurrent acquisition of the same polymorphism, G743A, on diverse genetic backgrounds as described earlier.
Virtually identical HA sequences
EU148428 A/chicken/Nigeria/1071-23/2007
EU148372 A/chicken/Nigeria/1071-4/2007
EU148380 A/chicken/Nigeria/1071-5/2007
EU148396 A/chicken/Nigeria/1071-9/2007
Closely related HA sequences
EU148356 A/chicken/Nigeria/1071-1/2007
EU148404 A/chicken/Nigeria/1071-10/2007
EU148412 A/chicken/Nigeria/1071-15/2007
EU148420 A/chicken/Nigeria/1071-22/2007
EU148436 A/chicken/Nigeria/1071-29/2007
EU148444 A/chicken/Nigeria/1071-30/2007
More distantly related HA sequences
EU148364 A/chicken/Nigeria/1071-3/2007
EU148388 A/chicken/Nigeria/1071-7/2007
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