H5N1 Linking Northern China to Southern Egypt
Recombinomics Commentary 15:20
April 9, 2008
The full H5N1 sequence from a tiger in Shanghai, A/tiger/Shanghai/01/2005(H5N1) is being released at Genbank. Several of the gene segments are related to clade 2.2 isolates including the HA sequence, which has the clade 2.2 (Qinghai) consensus cleavage site, GERRRKKR. The sequence has a number of polymorphism from northern China, but also has nine polymorphisms shared with a subset of clade 2.2 isolates. One is linked to isolates from northern Germany / Denmark, which a second is found in most clade 2.2.3 isolates. However, 7 of the 9 polymorphisms link to isolates in Egypt and this linkage is concentrated in isolates from southern Egypt which were associated with mild cases.
This linkage, including 2-3 shared polymorphisms per isolate, provides additional evidence for acquisitions via recombination. The Egyptian polymorphisms are on branches of an HA phylogenetic tree that emerged in 2007. The isolates have the Egyptian genetic background, but have appended new polymorphisms and the linkage to the Shanghai tiger ties the Egyptian acquisitions to northern China. Many of these isolates also have the Mongolian HA cleavage site, providing additional linkages to this geographical region.
These linkages seriously challenge the influenza genetics dogma, which relies of selection of random mutations to explain influenza evolution. The clustering of polymorphisms supports acquisition via recombination, rather than selective adaptation through random mutations. The number of new acquisitions in the Shanghai tiger sequence, as well as the 2007 Egyptian isolates is limited, which greatly discounts such acquisitions from a large pool of random mutations.
The acquisitions via recombination, and well defined distribution routes of these polymorphisms, allow for predictions of new acquisitions and applications for vaccine target selection.
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