Transmission bias mutations that are conserved or at high frequency in closely clustering human and avian isolates.

Conserved residues and residues with high-frequency amino acids in closely clustering human isolates which have significantly low probability to neutrally evolve from and significant differences in amino-acid frequencies from the entire avian viral pool of each geographical region and year. Frequencies for other significant mutations are in Table S3.aInformation on the function of residues is taken from Duvvuri et al. [11].bThe numbers in the rows next to each country's names indicate the number of samples in each class.cThe years of first report in each country as per the information available in the NCBI Influenza Virus Resource database.d“∼” indicates adjacent residue.eEpitope.fFrequency in percent.gReceptor-binding site.hGlycosylation site.iPolybasic cleavage site.jThe first human isolate of H5N1 reported was in 2003, but there was contiguous reporting of human isolates only since 2005.k3 residues upstream.