JN.1.16 got S:Q493E ( 2 GBW samples, 1 patient, Taiwan) after triple nuc mutation Orf7a:F59K

[FedeGueli]

Jn.1.16 seems to have acquired S:Q493E in Taiwan

Defining mutations: Jn.1.16 >> A532G, Orf1a.G400S (G1463A) > Orf7a:F59K (T27568A, T27569A, T27570A) > C4543T, A14475G, S:S31P (T21653C), S:Q493E (C23039G), N:P279S (C29108T), C29353T Query: A532G, G1463A,C4543T Samples: 2 (same patient, GBW-Taiwan) Tree:

https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice1_genome_test_25fe2_9242c0.json?label=id:node_11520302 (Edited) Thx @ryhisner Ryan for highlighting the belgian sample belonging to the parent of this lineage

[ryhisner]

ORF7a:F59K is a really bizarre mutation—it's a triple T->A mutation. T->A is the third-rarest type of nuc mutation, so there's no way this happened stepwise. It's happened numerous times independently throughout the pandemic, so I have no doubt that it's real. There are now 50 sequences total with ORF7a:F59K that I think are legit.

There are other double-A or triple-A mutations but they usually fit one of a number of patterns, the main ones being TRS-like motifs and recombination with the region just before the N start codon. This one doesn't fit either pattern. However, with it, 25764-25774 makes for a perfect reverse complement of an 11-nucleotide stretch in NSP6 (11131-11141). I regard stretches of 8-9 nucleotides as likely being coincidental, but 11 nucleotides is unlikely to be a coincidence.

So my guess is that this triple-T->A mutation is due to recombination with this this region of NSP6, though I don't feel overly certain about that.

It's also worth noting that there's a second stretch of nucleotides, 7593-7602, that forms the ORF7a:F59K region forms a perfect reverse complement with over a 10-nucleotide stretch, which again is more than you'd expect to find by coincidence.

[FedeGueli]

thank you Ryan!