"Mutation" in the sense of a single subtype stochastically accumulating mutations to its own genome is not what causes the emergence of most new pathogenic subt

"Mutation" in the sense of a single subtype stochastically accumulating mutations to its own genome is not what causes the emergence of most new pathogenic subtypes - its antigenic drift via genomic reassortment in co-infected hosts. New subtypes / serotypes that are highly pathogenic to humans usually develop when multiple different subtypes co-infect and replicate in the same cell of an infected host. This can lead to "reassortment" of the genes in pool of replicating viral genomes. Most of the time when this happens the resulting hybrid genomes are probably too screwed up to be viable, but sometimes it leads to new genomic assortments that are viable and remix the pathogenic genes of one donor subtype with the surface coat proteins of a different subtype, resulting in a new subtype that is both pathogenic and antigenically novel to the host species. This is why we need to constantly make new influenza vaccines as fast as possible. This page explains it better than I did: "Influenza A viruses have eight separate gene segments. The segmented genome allows influenza A viruses from different species to mix and create a new virus if influenza A viruses from two different species infect the same person or animal. For example, if a pig were infected with a human influenza A virus and an avian influenza A virus at the same time, the new replicating viruses could mix existing genetic information (reassortment) and produce a new influenza A virus that had most of the genes from the human virus, but a hemagglutinin gene and/or neuraminidase gene and other genes from the avian virus. The resulting new virus might then be able to infect humans and spread easily from person to person, but it would have surface proteins (hemagglutinin and/or neuraminidase) different than those currently found in influenza viruses that infect humans. This type of major change in the influenza A viruses is known as “antigenic shift.” Antigenic shift results when a new influenza A virus subtype to which most people have little or no immune protection infects humans. If this new influenza A virus causes illness in people and is transmitted easily from person to person in a sustained manner, an influenza pandemic can occur." - https://www.cdc.gov/flu/avianflu/virus-transmission.htm https://www.cdc.gov/flu/avianflu/virus-transmission.htm