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H5N1 H7N1 PB1 Recombination in Hubei Northern China
October 6, 2006
New H5N1 sequences have been released from northern China. In several instances these are sequences from earlier isolates which were originally submitted to GenBank by the Beijing Genome Institute on February 28, 2005 under the title, “A cohort of AIV H5N1 subtypes isolated from wild aquatic birds and domestic poultry revealed rapid transmission, frequent reassortment, and identifiable recombination events.” One of the sequences with clear cut homologous recombination was A/chicken/Henan/210/2004(H5N1). The re-sequenced sample, A/chicken/Henan/wu/2004(H5N1) is identical in 7 of the 8 gene segments. The sole difference was in PB2 and the new sequences which removed the premature termination codon. The new sequence confirms the previously identified recombination.
However, the recombination in northern China was not limited to sequences generated by the Beijing Genome Institute. A recent paper by Harbin Veterinary Research Institute and St Jude described the relationship between an H7N2 isolate from a chicken in Hubei in 2002, A/chicken/Hubei/1/2002(H7N2), and a 1979 H7N1 isolate from an African starling, from a quarantined bird in England, A/African starling/England-Q/983/1979(H7N1). Those sequences however had a region of identity with a 2001 H5N1 chicken sequence, A/chicken/Hubei/718/2001(H5N1) generated by the China Agricultural University in Beijing. The sequence between positions 1729 and 2182 of the 1979 and 2001 isolates were identical, even though the two PB1 sequences were only 93% homologous.
The region of identity between the two PB1 sequences strongly supports acquisition via homologous recombination, and the identity between the sequences that were 22 years apart shows that the sequence could be faithfully copied over an extended time period. These data were similar to Canadian swine data which also had examples of clear cut recombination as well as long stretches of identity in sequences that were isolated over 25 years apart (see identities in PB2 and PA).
The examples of frequent and clear cut homologous recombination involving sequences faithfully copied for several decades seriously challenges the dogma of influenza genetic which maintains that seasonal variations are due to genetic drift cause by random mutations generated by a polymerase lacking a proof reading function and pandemic shifts are due to reassortment.
The latest examples of recombination show that the random muations can easily be generated by homologous recombination between closely related sequences, and genetic shifts can be generated by recombination between distantly related genes. The acquisition of single nucleotide changes (SNPs) by homologous recombination is also supported by polymorphism tracing through an expanding sequence database. The “new: polymorphisms are easily found in earlier sequences which are frequently found in closely related sequences which are transported and transmitted by wild birds.