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bioRxiv · 10.64898/2026.07.08.737272

Three phylogenetic metrics are compatible with natural evolution of the earliest SARS-CoV-2 sequence

Lorenzi, J.-N.·Graner, F.·Bigot, T.·Decroly, E.·Courtier-Orgogozo, V.·Achaz, G.
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Abstract

Comparative analyses of coronavirus sequences can unravel important aspects of their complex evolution. Here we develop a method to infer past recombination breakpoints based on minimizing homoplasies count. We test it on three outbreak viruses (SARS-CoV-1, MERS-CoV, and SARS-CoV-2) and various chimeric coronaviruses as positive controls. We identify genomic regions evolving under distinct selective pressures. We also trace possible signs of human-made manipulations using metrics such as synonymous and non-synonymous mutation rates, codon usage and insertion patterns. Our pipeline appears to efficiently detect synthetic sequence optimization or genome re-encoding, but does not identify chimeras of natural viruses. Unlike in positive controls, with our method no signal of human-made manipulation is detected in SARS-CoV-1, MERS-CoV, nor SARS-CoV-2.

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Lorenzi, J.-N., Graner, F., Bigot, T., Decroly, E., Courtier-Orgogozo, V., Achaz, G.. 2026-07-14. Three phylogenetic metrics are compatible with natural evolution of the earliest SARS-CoV-2 sequence. https://doi.org/10.64898/2026.07.08.737272

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