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bioRxiv · 10.1101/2020.05.28.122366

Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans

MacLean, O. A.·Lytras, S.·Singer, J. B.·Weaver, S.·Kosakovsky Pond, S. L.·Robertson, D. L.
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Abstract

RNA viruses are proficient at switching host species, and evolving adaptations to exploit the new hosts cells efficiently. Surprisingly, SARS-CoV-2 has apparently required no significant adaptation to humans since the start of the COVID-19 pandemic, with no observed selective sweeps since genome sampling began. Here we assess the types of natural selection taking place in Sarbecoviruses in horseshoe bats versus SARS-CoV-2 evolution in humans. While there is moderate evidence of diversifying positive selection in SARS-CoV-2 in humans, it is limited to the early phase of the pandemic, and purifying selection is much weaker in SARS-CoV-2 than in related bat Sarbecoviruses. In contrast, our analysis detects significant positive episodic diversifying selection acting on the bat virus lineage SARS-CoV-2 emerged from, accompanied by an adaptive depletion in CpG composition presumed to be linked to the action of antiviral mechanisms in ancestral hosts. The closest bat virus to SARS-CoV-2, RmYN02 (sharing an ancestor [~]1976), is a recombinant with a structure that includes differential CpG content in Spike; clear evidence of coinfection and evolution in bats without involvement of other species. Collectively our results demonstrate the progenitor of SARS-CoV-2 was capable of near immediate human-human transmission as a consequence of its adaptive evolutionary history in bats, not humans.

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MacLean, O. A., Lytras, S., Singer, J. B., Weaver, S., Kosakovsky Pond, S. L., Robertson, D. L.. 2020-05-29. Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans. https://doi.org/10.1101/2020.05.28.122366

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