California herpes dating

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Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years.The primate simplex viruses exemplify this pattern of virus–host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes.Scenarios Although host–virus codivergence is the primary mode of evolution for primate simplex viruses, zoonotic transmission can occur. For viruses such as HIV and influenza A virus, whose evolutionary rate is on the order of 10 substitutions/site/year, it is standard to rely on t MRCA estimates around 100 years old (Korber et al. The standard evolutionary models produce dating estimates that are not consistent with any of the ten evolutionary origin scenarios.For example, humans are frequently infected by a macaque simplex virus (MHV-1, formerly known as B virus) (Elmore and Eberle 2008), resulting in severe illness, though human-to-human transmission is exceptionally rare (Centers for Disease Control and Prevention 1987). In the case of human herpes simplex viruses, molecular sequence dating could be used to identify which divergence event (i.e., HSV-1/Ch HV or HSV-2/Ch HV) corresponds to the speciation between around 6 Ma (Kumar et al. Previous dating analysis accompanying the discovery of Ch HV used pairwise genetic distance regression analysis to suggest that HSV-2 was the result of codivergence 6 Ma and that HSV-1 originated from an orangutan cross-species transmission event (fig. In contrast, our selection-informed model suggests a new explanation for the origin of human herpes simplex viruses, in which HSV-2 was acquired by an extinct species from an ancestor of modern chimpanzees.5) branch length instead of the expanded length for this branch in our subsequent analyses, the hypothesis testing results and t MRCA inference remained unaffected (not shown).We inferred the t MRCAs of HSV-1/Ch HV and HSV-2/Ch HV under the BSREL substitution model and investigated which of the ten alternative hypotheses was most consistent with these estimates.

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Scenarios Evolutionary scenarios that could produce the human and chimpanzee herpes simplex virus phylogeny via viral cross-species transmission. Nodes representing the common ancestor of humans and chimpanzees, around 6 Ma, are indicated with asterisks. However, such analyses may be misleading because, unlike phylogeny-based molecular clocks, they do not account for shared evolutionary history (Drummond et al. Recent methodological developments in the dating of RNA viruses have suggested that standard evolutionary models used in molecular dating can underestimate the time to most recent common ancestor (t MRCA) (e.g., in measles virus, Ebola virus, avian influenza virus, and coronaviruses) (Wertheim and Kosakovsky Pond 2011; Wertheim et al. This bias has been attributed to the action of strong purifying selection over long evolutionary time scales, and selection-informed models have been shown to improve branch length estimation (Wertheim and Kosakovsky Pond 2011); even under these models, however, many viruses are likely too old to produce reliable t MRCA estimates. To resolve the origin of HSV-1 and HSV-2, we propose a novel computational hypothesis testing approach that combines realistic codon-substitution evolutionary models that allow for selection strength heterogeneity with a penalized likelihood molecular clock estimation procedure.To more accurately estimate ancient viral divergence times, we applied a branch-site random effects likelihood model of molecular evolution that allows the strength of natural selection to vary across both the viral phylogeny and the gene alignment.This selection-informed model favored a scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose from a cross-species transmission event from the ancestor of modern chimpanzees to an extinct precursor of modern humans, around 1.6 Ma.General pattern of codivergence for primate herpes simplex viruses and their Simiiforme hosts.Underlined viral taxa indicate phylogenetic incongruence, implying cross-species transmission events. General pattern of codivergence for primate herpes simplex viruses and their Simiiforme hosts. HSV-2 is more closely related to Ch HV than it is to HSV-1, which suggests that Ch HV and at least one of the human herpes simplex viruses arose via host–virus codivergence.

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