Convergent mutations and their hot spots. (A) Distribution of convergent mutations in cluster 1 (comprising samples primarily from Japan). Convergent SNVs are illustrated in red, whereas other SNVs are in gray. (B) Classification of convergent and other SNVs. Synonymous SNVs were less frequent among convergent SNVs compared with other SNVs. (C) Distribution of convergent SNVs within EBNA3B. (D) Amino acid substitutions resulting from convergent SNVs in the core central homology domain of EBNA3B. Identical amino acids among the 3 EBNA3 homologs are illustrated in red and green. Blue and yellow lines represent predicted antigenic peptides and critical residues for RBP/J binding, respectively. (E) Mutual exclusivity of convergent SNVs in the EBNA3B core central homology domain. Ten distinct SNVs (each affecting 2-35 samples) were distributed across 91 samples without any overlap. (F) Monte Carlo simulation of mutual exclusivity. Random distribution of 10 distinct SNVs across 366 samples (in cluster 1) resulted in the expectation that some samples might harbor 2 or more SNVs. Under 10 million simulation trials, the likelihood of no overlap was calculated as 4.92 × 10−5. (G) Convergent SNVs affecting LMP1. A relatively large number of convergent SNVs were found within the transmembrane (TM) 2 domain. (H) Amino acid substitutions from convergent SNVs in the TM 2 domain. Hydrophobic amino acid residues are indicated in red. (I) Convergent SNVs upstream of LMP1. Among the 3 known promoters, pED-L1 was most frequently affected by convergent SNVs. (J) Convergent SNVs in EBNA3A. The upper histogram illustrates convergent SNVs found in cluster 1 (mainly Japan), whereas the lower histogram illustrates those found in cluster 2 (mainly China). GC, gastric carcinoma.
