Abstract
Estimating viral timescales is fundamental to understanding the evolutionary biology of viruses. Molecular clocks are widely used for revealing their recent evolutionary histories but may severely underestimate their longer-term origins. This is because inferred rates of evolution are inversely correlated to the timescale of their measurement1,2. This rate decay is well described by a power law with a slope of -0.65 and can be observed across all known viral genome types3, implying a common process. We provide the first predictive mechanistic model that can readily explain the pattern of rate decay over a wide range of timescales and recapitulates the ubiquitous power-law rate decay with a slope of -0.65 (95% HPD: -0.72, -0.52). We show that standard substitution models fail to correctly estimate divergence times once the most rapidly evolving sites saturate, typically after hundreds of years in RNA viruses and thousands of years in DNA viruses, whereas we can successfully re-create the observed pattern of decay and explain the evolutionary processes involved in creating the time-dependent rate phenomenon. We apply our model to re-date the diversification of genotypes of hepatitis C virus (HCV) to 396,000 (95% HPD: 326,000 - 425,000) years before present, a time preceding the dispersal of modern humans out of Africa, and also showed that the most recent common ancestor of sarbecoviruses dates back to 23,500 (95% HPD: 21,100 - 25,300) years ago, nearly thirty times older than previous estimates4. This not only creates a radical new perspective for our understanding the origins of these viruses, but also suggests a substantial revision of evolutionary timescales of other viruses can be similarly achieved.
Highlights
The timescale over which viruses evolve and how this process is connected to host adaptation has been an area of considerable research and methodological progress in recent decades
Inferred short-term rates of virus sequence change should create completely unrecognizable genome sequences if they were naively extrapolated over thousands, or even hundreds, of years, yet endogenous viral elements (EVEs) that integrated into host genomes throughout mammalian evolution are recognizably similar to contemporary genera and families of Bornaviridae, Parvoviridae, and Circoviridae, among many other examples.[13,14,15]
This observation is complemented by evidence from studies of virus/host co-evolution[16,17,18] and, more recently, from analyses of viruses recovered from ancient DNA and RNA in archaeological remains,[19,20,21,22] which indicate a remarkable degree of conservation in viral genome sequences and their interrelationships at genus and family levels
Summary
The timescale over which viruses evolve and how this process is connected to host adaptation has been an area of considerable research and methodological progress in recent decades. Inferred short-term rates of virus sequence change should create completely unrecognizable genome sequences if they were naively extrapolated over thousands, or even hundreds, of years, yet endogenous viral elements (EVEs) that integrated into host genomes throughout mammalian evolution are recognizably similar to contemporary genera and families of Bornaviridae, Parvoviridae, and Circoviridae, among many other examples.[13,14,15] This observation is complemented by evidence from studies of virus/host co-evolution[16,17,18] and, more recently, from analyses of viruses recovered from ancient DNA and RNA in archaeological remains,[19,20,21,22] which indicate a remarkable degree of conservation in viral genome sequences and their interrelationships at genus and family levels This dichotomy has been attributed to the time-dependent rate phenomenon (TDRP), which is the observation that apparent rates of evolution are dependent on timescales of measurement.[23,24]
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