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Commentary
Identical H1N1 Fatal
D225G Sequences in Brazil and Ukraine
Recombinomics
Commentary 14:39
January 11, 2010
However, the sequence in the July sample from Brazil was an exact match with A/Lviv/N6/2009, which was from the lung of a fatal case in Ukraine, collected in late October. This identity provides additional evidence supporting the spread of these sequences, which is further supported by matches between more localized sequences.
However, the WHO working hypothesis maintains that the changes at position 225 are random errors that do not transmit. The matches such as the one above, or the same change in closely related sequences that are close in time and space, are simply coincidences generating independently again and again by copy errors. This unlikely scenario is cited because these changes are appended onto different genetic backgrounds. In Brazil the background in Rio de Janeiro with D225G is distinct from the two sequences in Sao Paulo with D225G. Moreover, there have been many additional examples of jumps from one genetic background to another, which is most easily explained by recombination. However, WHO consultants insist that recombination plays little or no role in genetic drift, which is solely driven by random copy errors.
As more data accumulates, this random mutation hypothesis becomes less and less tenable. In addition to the above sequence from Brazil, recent sequences from Ukraine and Moldova have two or more changes at position 225, further diminishingly the explanation of random mutations. In Ukraine, these new sequences demonstrated that the reports of position 225 changes paralleled the spread of the outbreak and associated fatalities. Initial sequences were from western Ukraine and involved HA sequences with D225G or D225N. Subsequent sequences from Kviv and Chernihiv had both changes in the same patient, which would require two random errors that coincidently targeted the same position in the same patient. Moreover, the Kyiv patient also has D225A requiring three random errors at the same position. Examples of multiple changes at the same position in the same patient have been reported in patients in the United States, Mexico, and Sweden, which are unlikely to be generated by the same random errors repeated again and again.
These changes are associated with a case fatality rate of 100% in many countries, including Ukraine and Brazil and raise serious concerns. The WHO effort of shoring up an untenable hypothesis is hazardous to the world's health.
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