Recombination Analysis In Human Influenza
Recombinomics Commentary 18:48
March 26, 2008
Using an exhaustive search and a nonparametric test for mosaic structure, we identified 315 sequences (~2%) in five different RNA segments that, after a multiple comparisons correction, had statistically significant mosaic signals compatible with homologous recombination.
More controversial, however, is the occurrence of homologous recombination in influenza viruses, most likely involving copy-choice (template-switching) replication of RNA molecules that co-infect a single cell. Although bioinformatic evidence for homologous recombination has been suggested (13, 19), these results remain unsubstantiated, with extensive lineage-specific rate variation a likely source of a false-positive signal for at least some putative recombination events (24, 31).
The above comments from the upcoming paper, “Homologous Recombination is Very Rare or Absent in Human Influenza A Virus”, describe the detection of small stretches of genetic information consistent with homologous recombination. The comments also note the presence of much longer regions of recombination in Canadian swine, although the possibility of differential evolution within a gene is cited as an explanation for the differential patterns of polymorphisms.
However, the differential evolution was discounted in the swine paper, because much of the divergence exactly matched early swine isolates and the crossover points varied, signaling independent recombination events.
The paper on the human influenza sequences however, failed to find longer stretches of recombination. Only two examples were found, and the authors suggest those two examples may have been due to contamination and the recombinant sequences may have been generated during amplification.
However, the detection of longer examples of recombination was limited by restrictions on the dataset being tested. Only full human sequences were used, which excluded sequences with clear examples of recombination. Moreover, the requirement of full sequences eliminated one set of parental sequences for the recombinants
The clear recombination involved a series of six HA sequences from Korea in 2002. The first and last third of the gene match contemporary H3N2 sequences, but the middle third of the genes match HA from sequences from isolates collected a decade earlier. The earlier origin, and the small differences in the recombined region of the six isolates reduced the likelihood that the recombined region was due to laboratory contamination.
In addition, the analysis did not include swine or avian sequences, which are frequent donor sequences for seasonal flu. Since the study focused on the recombinant as well as both parental sequences, the exclusion of swine and avian sequences would further reduce the number of recombinants identified using the criteria in the paper.
Similarly, the paper did not analyze recombination in avian or swine influenza.
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