Fig4: Non-homogeneous models of influenza evolution. All model trees are unrooted. The real root is assumed to lie somewhere along the avian branches, however, its position is irrelevant since stationary evolution of the virus in the avian host is being assumed. Model M1 is homogeneous and the host shift event (HSE) cannot be determined. In models M2 and M3 the HSE is assigned avian equilibrium frequencies. Different shadings indicate that different rate matrices (equilibrium nucleotide frequencies) are used to describe evolution along the corresponding branches. With current data it is not possible to distinguish whether the HSE was avian to human, or avian to swine, so model M3 is in reality two models according to whether the branch linking the human–swine split (HSS) and the HSE is assigned human (M3h) or swine (M3s) equilibrium frequencies. Model M2.2J assumes two independent host shifts bird to mammal (see text)

Mentions: Using different sets of π values to describe the evolution along different branches of the tree implies time heterogeneity in the substitution pattern. In this work, we considered three models of evolution in the human–swine–avian tree (Fig. 4). The first model (M1) assumed homogeneity and stationarity, with one set of equilibrium nucleotide frequencies describing the substitution process in all branches of the tree. The second model (M2) assumed that equilibrium nucleotide frequencies are different in mammalian and avian hosts. The third model (M3), assumed different sets of equilibrium nucleotide frequencies for avian, human, and swine hosts, with the initial avian to mammal host shift occurring either to swine (M3s) or to humans (M3h). In models M2 and M3, evolution along the avian clade is stationary. Models M1, M2, and M3 are nested, so their log-likelihoods can be compared with the likelihood ratio test (LRT) to select the best model. The three models described above assumed a single avian to mammal host shift event. A variation of the M2 model was also tested that assumes that influenza was transmitted independently from birds to humans and from birds to swine following the divergence of these two lineages (M2.2j, Fig. 4). This model is not nested with any of the other models so the LRT cannot be used to assess its adequacy; the Akaike Information Criterion (AIC) can be used instead (Akaike 1974). All the models were tested on the data above using a nonhomogeneous implementation of the HKY85 model (PAML v3.15; Yang 1997; Yang and Roberts 1995) that considers rate variation among sites as a discrete gamma distribution (Yang 1996). A single gamma shape parameter (α) was assumed for the whole tree. Consideration of rate variation is fundamental since nucleotide frequencies decay at different rates at different sites, and averaging over them would lead to underestimation of the branch linking the mammalian clade with the host shift event.Fig. 4

dos Reis M, Hay AJ, Goldstein RA - J. Mol. Evol. (2009)

Bottom Line: The viruses later diverged into the classical swine and human H1N1 influenza lineages around 1913-1915.The last common ancestor of human strains dates from February 1917 to April 1918.This would suggest that the virus was introduced into humans sometime between 1913 and 1918.

Affiliation: The MRC National Institute for Medical Research, London, NW7 1AA, UK. m.reis@mail.cryst.bbk.ac.uk

Abstract: Nonhomogeneous Markov models of nucleotide substitution have received scant attention. Here we explore the possibility of using nonhomogeneous models to identify host shift nodes along phylogenetic trees of pathogens evolving in different hosts. It has been noticed that influenza viruses show marked differences in nucleotide composition in human and avian hosts. We take advantage of this fact to identify the host shift event that led to the 1918 'Spanish' influenza. This disease killed over 50 million people worldwide, ranking it as the deadliest pandemic in recorded history. Our model suggests that the eight RNA segments which eventually became the 1918 viral genome were introduced into a mammalian host around 1882-1913. The viruses later diverged into the classical swine and human H1N1 influenza lineages around 1913-1915. The last common ancestor of human strains dates from February 1917 to April 1918. Because pigs are more readily infected with avian influenza viruses than humans, it would seem that they were the original recipient of the virus. This would suggest that the virus was introduced into humans sometime between 1913 and 1918.