When I first posted on this topic Dec 12, 2021, the additional Omicron variant BA.3 was not available to me for analysis. Recently, Dr. William Haseltine has published a very useful Venn diagram, showing the regions of overlap in mutations among BA.1, BA.2 and BA.3 (1). From the pattern it is evident that BA.3 is overwhelmingly a multiply recombinant derivative of both BA.1 and BA.2, with only a single unique mutation.
The pattern of shared vs. unique mutations in the component proteins of Orf1a suggest multiple crossovers between early versions of BA.1 and BA.2 in what I defined above as Segment A, the first 10kb of the genome. Segment A therefore does not behave as a genetic monolith in recombination, but multiply reassortable sub-segments.
There are unique mutations in Segment B that may have arisen after the recombination events that produced BA.3, but not enough to suggest additional recombination within Segment B.
Segment C, much of the N-terminal domain of BA.3, appears to be derived from BA.1. Segment D is common, but what I speculated might be Segment E (the structural core of RBD prior to the RBM) appears to be validated by being derived in BA.3 from BA.2, before the many common RBM mutations among all three sub-variants.
There is still too little mutation downstream to validate recombination events after S, as the few could easily arise after the recombination events yielding the three sub-variants had taken place.
One further note. These variants are being compared to one another and to other variants in phylogenetic trees. Strictly speaking, recombinants presented that way introduce erroneous evolutionary relationships, since substantial portions of each do not have common parentage. BA.3 is not really divergent at all, in that it has only a single unique mutation. Throughout its genome it is virtually identical to either BA.1 or to BA.2, a chimera with virtually no unique RNA of its own.
The best analogy may well be Legos of different colors, representing independently evolved genetic units. As a child might select a red piece, then a green, then a blue, each from a different bin, and hook them together in a line, coronaviruses have done with RNA for as long as we can observe from their wide range of sub-families and many variants.
Unfortunately, the number of genetically independent bins of RNA Legos appears to be quite large (2).
Bill Gallaher
(1.) Haseltine, W.A. Birth Of The Omicron Family: BA.1, BA.2, BA.3. Each As Different As Alpha Is From Delta. (forbes.com)
(2.) Boni MF, Lemey P, Jiang X, Lam TT, Perry BW, Castoe TA, Rambaut A, Robertson DL. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. Nat Microbiol. 2020 Nov;5(11):1408-1417. doi: 10.1038/s41564-020-0771-4. Epub 2020 Jul 28. PMID: 32724171.