Random Mutation, Reassortment, and Recombination
 
The nomenclature used to discuss flu evolution can be quite confusing.  This is an attempt to make some of the terms clear so that we may avoid confusion.
 
A reminder - influenza has a segmented genome. There are eight genomic segments made of single stranded RNA. This RNA is composed of nucleotides. There are typically over a thousand nucleotides in each segment. Changes in the RNA can result in changes in viral proteins which may result in changes in the function of the virus.
 
Random mutation - fairly self-explanatory. May have a number of causes including inaccurate copying of genes by the polymerase complex. These changes usually are small, most often a single nucleotide. Such small changes are thought to result in Antigenic Drift if they result in small changes in the HA gene. This allows flu viruses to partially escape our immune system. This is the reason we need a new flu shot every year.
 
Reassortment - Exchange of entire genes between two flu viruses. This requires co-infection of a cell with 2 different viruses. Exchange of HA genes between different subtypes is thought to have been the cause of the last 2 pandemics. This large change is referred to as Antigenic Shift.
 
Recombination - This term actually has several meanings. In a general sense, it simply means the combination of nucleotides from different sources. Reassortment is thus one example of recombination. In fact, many papers with the term “recombination” in them are actually referring to reassortment. Further, genetic engineers use the term “recombinant” to refer to viruses that they have artificially constructed in the lab. This is actually the way that the term is most frequently used. However, when a distinction is made between reassortment and recombination, recombination usually means an exchange of a subset of nucleotides of one genomic segment.  For example, the first 700 nucleotides of an HA gene may be identical to an HA gene from one virus while the remaining 1000 nucleotides may be identical to a HA gene from a different virus. As in reassortment, co-infection of two different strains or subtypes is required.
 
Recombination may be either homologous or non-homologous. The former occurs when the recombination occurs between the same gene or nucleotide segment. The latter occurs when two different genes are involved. Homologous recombination occurs during meiosis.