In creating the supermap, researchers studied genetic data from 351 isolates of the virus. They were especially interested in discovering if certain hosts were carrying specific forms of the virus and which viruses carried specific mutations enabling transmission to humans.
"We found the visualization of multiple layers of information very helpful in generating hypotheses we could test through statistical analysis of the mutation data we organized in the evolutionary tree," says Janies. "The findings helped us understand whether mutations that appear to be associated with certain hosts or geographic regions appeared by chance, or whether they were true adaptations of the virus as it spread."
Flu viruses are classified according to several criteria: whether they come from animals or humans, and the activity of two key proteins that sit on the surface of the virus, hemaglutinin (HA), and neuraminidase (NA). HA helps the virus "stick" to a host cell and infect it; NA helps the virus escape from the cell and spread to other cells and hosts. In the past, scientists hypothesized that if a strain of the virus emerged that enabled human-to-human transmission, it would probably involve mutations in these two proteins.
Janies and his colleagues did not find any genotypes associated with mutations in these two surface proteins that were significantly associated with any specific type of host. They did, however, find a strong association between a specific genotype (Lysine-627 in the polymerase basic protein of the virus) and mammalian hosts in the field.
"While this genotype is not exclusive to mammals, we think it is important to track how this particular mutation is spreading because it appears to be so infective and deadly in mice," says Janies.