Adaptation and convergent evolution of SARS-CoV-2 and other human RNA viruses

Richard Neher
Biozentrum & SIB, University of Basel

slides at

Available data on Jan 26 2020

Early genomes differed by only a few mutations, suggesting very recent emergence

Emergence and dominance of VoCs

Real-time tracking on Nextstrain

VoCs have more mutations than expected...


VoCs and VoIs: rapid converging evolution by Emma Hodcroft

VoCs have been replacing other strains quickly

S-gene positivity in the UK
Althaus et al, 2021, PHE Technical Briefing

SARS-CoV-2 variants can become dominant without transmission advantage

  • Large differences in incidence (Spain vs most of Europe in Summer 2020)
  • High travel volume during summer 2020
  • Demographics with more social contacts
Hodcroft et al

How do we tell early on whether a variant is concerning?

How unusual are the patterns of convergent evolution?

Convergent evolution is common in RNA viruses

Influenza A/H3N2:

4-fold convergence at positions 142 and 193 of HA1

  • Convergent evolution is a tell-tale sign of adaptation
    (hitting the same site by chance is unlikely)
  • But: RNA viruses are not mutation limited
  • In suitable environments, homoplasies are common
  • Variation at homoplasic positions is often selected
    → but success depends on background

Convergent evolution is common in RNA viruses


  • Convergence at positions 186 and 189
  • Ferret serology is rather insensitive to these changes, but very sensitive to 156K

Mutational signatures

Number of amino acid changes in the S1 domain
Prominent deletions the spike NTD
Common convergent deletion in NSP6

Growth measures and experimental scores

Recent growth rate
RBD escape based on deep mutational scanning.
Allie Greaney (Jesse Bloom's lab)

Deep mutational scanning for RBD mutations that affect AB binding and ACE2 binding


  • Since late 2020, dominance of variants with abundant changes in Spike
  • So far, successful variants had increased transmissibility, not immune escape
    → Beta, Gamma, and Mu are driven out by Delta
  • We expect a gradual shift to selection for immune escape
  • Prior to Delta, success of variants was regional. Delta is successful across the globe
Zhou et al, 2021


Trevor Bedford and his lab -- terrific collaboration since 2014

especially James Hadfield, Emma Hodcroft, Ivan Aksamentov, Moira Zuber, John Huddleston, and Tom Sibley

Data we analyze are contributed by scientists from all over the world

Data are shared and curated by GISAID