Table 2. Discordantly evolving sites of the SARS-CoV-2 S-protein.

The following characteristics are shown: coordinates on the S-protein sequence, nominal p-values, the value of the epistatic statistic, the total number of consecutive mutation pairs for the two corresponding ordered site pairs, numbers of mutations in consecutive pairs at site 1 and site 2, total numbers of mutations at site 1 and site 2, FDR value corresponding to the p-value of the site pair obtained for the alternative phylogeny reconstructed by UShER (Turakhia et al., 2021), and the distance in the protein structure (PDB ID: 7JJJ). Pairs of sites where non-consecutive mutations are closer to each other than expected (suggesting both epistatic and episodic selection; p-value <0.05 after adjustment) are in bold; those where they are further from each other than expected (suggesting episodic rather than epistatic selection) are in italic (see Appendix 1—tables 11 and 13).

site 1	site 2	p-value	epistat.	#consec. pairs of mutations	#mut. in consec. pairs in site1	#mut. in consec. pairs in site2	#mut. in site1	#mut. in site2	FDRUShER tree	physical distance,Å
69	614	3e-3	0.07	5	1	5	5	14	0.231	46.75
222	501	3.1e-3	0.01	1	1	1	11	40	0.058	55.44
440	681	3.1e-3	0.01	1	1	1	12	59	0.055	-
501	675	1.2e-3	0.02	1	1	1	40	24	0.06	84.98
501	677	4.8e-4	0.05	3	2	3	40	39	0	88.20
570	614	2.4e-3	0.16	7	1	7	16	14	0.895	19.30
614	653	4e-5	0.03	4	1	4	14	5	0.025	15.47
614	982	3.2e-4	0.12	7	1	7	14	15	0.891	27.87
681	1176	3.9e-3	0.01	1	1	1	59	11	0.385	-