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The Data are Insufficient to Confidently Root the SARS-CoV-2 Phylogenetic Tree
1Fred Hutchinson Cancer Center, Howard Hughes Medical Institute, Seattle, WA 98103, USA.
Molecular Biology and Evolution
|June 9, 2025
Summary
The SARS-CoV-2 phylogenetic tree root remains uncertain due to biases in early viral sequences. Current data cannot conclusively determine the true evolutionary origin of SARS-CoV-2.
Area of Science:
- Virology
- Phylogenetics
- Genomic epidemiology
Background:
- Discrepancies exist between outgroup and date-based methods for rooting the SARS-CoV-2 phylogenetic tree.
- Previous work suggested potential biases in early viral sequences as a cause for these discrepancies.
Purpose of the Study:
- To explain the reasons for the uncertainty in rooting the SARS-CoV-2 phylogenetic tree.
- To provide evidence of bias in early SARS-CoV-2 sequences.
- To demonstrate why the root cannot be conclusively resolved with current data.
Main Methods:
- Analysis of early SARS-CoV-2 viral sequences.
- Comparison of outgroup and date-based phylogenetic rooting methods.
- Utilizing an interactive narrative to explore underlying data and discrepancies.
Main Results:
- Clear evidence of bias among the earliest available SARS-CoV-2 sequences was demonstrated.
- Different rooting methods yield different inferences about the SARS-CoV-2 root due to data discrepancies.
- The root of the SARS-CoV-2 tree cannot be conclusively resolved with the current dataset.
Conclusions:
- Biases in early SARS-CoV-2 sequences are a significant factor contributing to rooting uncertainty.
- The evolutionary origin of SARS-CoV-2 remains unresolved due to limitations in the available early sequence data.
- Further research with less biased sequence data is needed for definitive phylogenetic rooting.
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