Omicron from mice

Omicron, South Africa on November 24th, 2021

Omicron diverged from the B.1.1 lineage roughly in mid-2020

Mutations not found in:

Alpha, Beta, Gamma, and Delta

SARS-CoV-2 variants isolated from three chronically infected patients

The B.1.1 variants showed the highest sequence similarities to Omicron

Normal rate of mutations in spike protein RNA

∼0.45 mutations per month

During missing time for Omicron

27 mutations accumulated in spike protein RNA (in Branch O) during 18 months

∼1.5 mutations per month

∼3.3 times faster than the average rate of other variants

First hypothesis

Omicron could have “cryptically spread” and circulated in a population

Second hypothesis

Omicron could have evolved in a chronically infected COVID-19 patient

Third hypothesis

Omicron could have accumulated mutations in a nonhuman host and then jumped into humans

Mice

Evidence for a mouse origin of the SARS-CoV-2 Omicron variant

The rapid accumulation of mutations Omicron

Proximal origin occurred in humans or another mammalian host?

Omicron, 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage

Significantly different from the spectrum for viruses that evolved in human patients

Omicron spike protein sequence, stronger positive selection than that of any previous variants

Suggesting a possibility of host-jumping

Resembled the spectra associated with virus evolution in a mouse cellular environment

Mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts

(through enhanced spike protein binding affinity for the mouse cell entry receptor)

So

Omicron jumped from humans to mice,

rapidly accumulated mutations conducive to infecting that host,

then jumped back into humans,

indicating an inter-species evolutionary trajectory for the Omicron outbreak

Fortunately

Evolved to increase binging to mouse ACE2 receptors

Consistent with human immune escape

Consistent with upper airway adsorption

© 2021 The Authors. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press.