Similarly, we detected that in the Pedacoviruses, Embecoviruses, Sarbecoviruses, and Igacoviruses , detectable break-point densities were significantly higher in the beginning and ending 5 per cent of coding regions than in the middle 90 per cent of these regions (P < 0.05; permutation test; Table 2 ) with marginal significance observed in Nobecoviruses (P = 0.054; permutation test; Table 2 ).
It is noteworthy that the test result for the Pedacoviruses also approached significance (P = 0.079) but that for the Merbecoviruses displayed no such tendencies (P = 0.875; although it should be noted that, of the four datasets tested, this dataset had the lowest number of detected break points in the S gene).
When we repeated the test only considering GC contents within 10 nucleotides of recombination break points (20-nt window in Table 4 ), the significant associations between break-point positions and lower GC content in Sarbecoviruses and Pedacoviruses were strengthened, and additionally, marginally significant associations with lower GC contents (0.05 < P < 0.1; permutation test) were detected in Merbecoviruses and Embecoviruses ( Fig. 3 , Supplementary Fig.