The return of the “Mistigri” through the SARS-CoV-2 XBB.1.5 chimera
that predominated in 2023
Abstract
The number of SARS-CoV-2 recombinants identified during the pandemic has
increased since the era of Omicron variants, but XBB.1.5 (or Omicron
23A) is the first lineage comprised of hybrid genomes to predominate at
the country and global scales. Very interestingly, the XBB.1.5
recombinant, like the Marseille-4B subvariant (B.1.160/20A.EU2) and the
pandemic variant B.1.1.7 (20I/Alpha) previously, has its ORF8 gene
inactivated by a stop codon. XBB.1.5 was generated through two
successive main events: a recombination between SARS-CoV-2 of lineages
BA.2.10.1.1 (BJ.1) and BA.2 75.3.1.1.1 (BM.1.1.1) that generated the XBB
(22F) lineage; then ORF8 gene inactivation by a stop codon. We further
identified that a stop codon was present at 89 (74%) codons of the ORF8
gene in ≥1 of 15,222,404 genomes available in GISAID, and at 15 codons
(12%) in ≥1,000 genomes. Thus, it is very likely that stop codons in
ORF8 gene contributed on at least 3 occasions and independently during
the SARS-CoV-2 pandemic to the evolutionary success of a lineage that
became transiently predominant, most recently XBB.1.5. Such association
of gene loss with evolutionary success, which suits the recently
described Mistigri rule, is an important biological phenomenon very
unknown in virology while largely described in cellular organisms.