No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2

TLDR

COVID‑19 is caused by SARS‑CoV‑2, a virus that recently jumped from an uncharacterised animal reservoir to humans and may still be adapting, raising speculation that recurrent mutations (homoplasies) could increase transmissibility. The study formally tests whether any recurrent mutations in SARS‑CoV‑2 are significantly associated with increased viral transmission. The authors develop a phylogenetic index comparing descendant counts in sister clades with and without a specific allele and apply it to 46,723 genomes to assess transmission impact of recurrent mutations. No recurrent mutation was convincingly linked to higher transmissibility; the mutations appear neutral and mainly driven by host RNA editing, with no evidence of more transmissible lineages.

Abstract

Abstract COVID-19 is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised animal reservoir. Due to this recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any homoplasies observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we develop a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a curated set of recurrent mutations identified within a dataset of 46,723 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent mutations currently in circulation appear to be evolutionary neutral and primarily induced by the human immune system via RNA editing, rather than being signatures of adaptation. At this stage we find no evidence for significantly more transmissible lineages of SARS-CoV-2 due to recurrent mutations.