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Recombination in PA Gene of H1 Canadian Swine
Recombinomics Commentary
March 20, 2006
Earlier analysis of the PB2 sequences in seven recent H1 isolates from Canada indicated all seven were recombinants. In addition to having extensive regions of identity with each other, the sequences had long stretches of identity with earlier isolates,. The identity with Tennessee/24 was particularly striking because the region of identity was over 1600 BP in two of the isolates, and since the sequences were from collections that were over 26 years apart, the fidelity of copying was extraordinarily high and cast significant doubt on mechanisms of rapid evolution that required random mutations, which is the dominant mechanism invoked by influenza geneticists.
Extensive regions of homology in PB2 parellel regions of identity in the PA gene. The Tennessee sequence is present in 6 of the 7 recent (2003-2004) isolates (Listed below0, including Ontario/53518 which did not have homology in the PB2 gene. However, in PA the two sequences are identical between positions 25 and 1469. The regions of identity for the 6 sequences are listed below. The homology regions range from 598 BP to 1866 BP. The sequence between positions 992-1319 is identical in all six isolates, but identity in one or more is found from positions 25-2016. Maintenance of exact copies in this region for over 26 years indicates that that stable errors in copying are extremely rare.
The seventh sequence, Ontario/56626 has regions (25-176, 286-422, 493-596, 700-829) of identity with isolate 1976, which was isolated in 1931. The maintenance of these identities for over 70 years provides further evidence for extreme fidelity in influenza replication.
Distribution data indicate that most single nucleotide polymorphisms are not due to recent errors in copying, but are due to recombination with closely related sequences. The above regions of identity with Tennessee/24 in two genes in 6 isolates from 2003 and 2004 casts serious doubt on the role of random mutations in rapid evolution of influenza genomes.
These data also highlight the significant issues related to sequestering of H5N1 sequences in a private WHO database. WHO and their consultants are firmly committed to a “random mutation” explanation for genetic drift. This position has serious problems, as indicated by the genetic stability outlined above. The data dictate an immediate release of the sequestered sequences so they can be properly analyzed.
A/swine/Alberta/56626/03(H1N1)
A/swine/Ontario/11112/04(H1N1) identity between 721-1319
A/swine/Ontario/23866/04(H1N1) identity between 992-1745
A/swine/Ontario/48235/04(H1N2) identity between 150-2016
A/swine/Ontario/53518/03(H1N1) identity between 25-1469
A/swine/Ontario/55383/04(H1N2) identity between 589-1787
A/swine/Ontario/57561/03(H1N1) identity between 541-1817
A/Swine/Tennessee/24/77 (H1N1)
A/Swine/1976/31 (H1N1)
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