Host Dependent Evolutionary Patterns and the Origin of 2009 H1N1 Pandemic Influenza
Alexander Solovyov, Benjamin Greenbaum, Gustavo Palacios, W. Ian Lipkin, and Raul Rabadan?
Columbia Unoiversity; ?Simons Center for Systems Biology, Institute for Advanced Study; Center for Infection and Immunity and Columbia University
Accepted January 30, 2010.
This research note is distributed under the Creative Commons Attribution 3.0 License.
Abstract
The origin of H1N1pdm constitutes an unresolved mystery, as its most recently observed ancestors were isolated in pigs nearly a decade before it emerged in humans. One theory suggests imperfect surveillance of swine viruses caused the virus to be missed in swine herds. Other hypotheses point to the possibility of laboratory error or an avian intermediary. We show substitution bias classification identifies the host where a virus has been evolving. Comparing the evolution of H1N1pdm ancestors with other influenza viruses, we show the evolutionary history in unsampled years is similar to the evolution of other swine viruses, presenting evidence it emerged from unsampled herds.
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The equilibrium representing the dynamics of the pandemic from 2000 to its emergence clearly clusters with classical swine H1N1, strongly suggesting that it did indeed evolve in swine in the interval between its last common ancestor and its emergence. This is further demonstrated in the heat map shown in Figure 2, where patterns of nucleotide frequency segregate according to host species, with the hidden swine dynamics clustering in the same pattern as classical swine. In addition to showing a swine specific pattern, the rates are consistent with what one would expect from normal evolution over this period. One can contrast this with the emergence of the 1977 H1N1 virus, which is believed to have escaped from a lab [11]. In this case the virus showed very few changes from the time it disappeared from the population until it was next detected, implying a literally ?frozen? evolutionary pattern. Here we show that, not only was this virus evolving at a normal rate, but also that it was evolving in a manner consistent with the theory that it was replicating in swine over the unobserved interim. The fact that the ancestors of the H1N1 pandemic strain present similar evolutionary patterns as other swine viruses provides a strong evidence for the ?unsampled pig herd hypothesis?.
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Funding Information
The work of G. Palacios and W. I. Lipkin was supported by National Institutes of Health awards HL083850 and AI57158 (Northeast Biodefense Center - Lipkin). The work of A. Solovyov has been supported by the National Institutes of Health awards U54 AI57158 (Northeast Biodefense Center - Lipkin) and the Department of Defense. The work of R. Rabadan has been supported by awards from the Northeast Biodefence Center (U54-AI057158-Lipkin) and the National Library of Medicine (1R01LM010140-01).
