Figure 7. Evolutionary accessibility of mutations from current avian influenza PB2 sequences.

Distribution of mean nucleotide substitutions required to access all amino-acid mutations, previously characterized human-adaptive mutations, and top human-adaptive mutations identified in our deep mutational scanning. Mean nucleotide substitution is calculated by averaging over all avian influenza PB2 sequences collected from 2015 to 2018. Most previously characterized human-adaptive mutations are accessible by single nucleotide substitution, whereas many of the new adaptive mutations that we identified require multiple nucleotide substitutions. Mean nucleotide substitutions for each mutation are in Figure 7—source data 1.