Not all changes are created equal (antigenic drift)
To understand the major genetic changes that lead to a pandemic, it helps to first understand the minor genetic changes that produce new flu strains in each flu season. Like all living things, influenza makes small errors—mutations—when it copies its genetic code during reproduction. But influenza lacks the ability to repair those errors, because it is an RNA virus; RNA, unlike DNA, lacks a self-correcting mechanism. As a result, influenza is not genetically stable. Every generation is slightly different, and those differences accumulate as time passes.
That slow deviation is called antigenic drift, and it is the reason why it is necessary to reformulate flu vaccines every year (see figure below). Every flu season, the genetic make-up of the dominant strains from the prior year will have drifted, changing the surface structure of those strains just enough to diminish, or even destroy, the effectiveness of the previous year’s vaccine. Each winter, health authorities must make an educated guess which strains are likely to dominate in the next flu season. It takes six more months to develop and manufacture vaccines for chosen strains. But in some years, genetic drift during just those six months can render the newly formulated vaccine ineffective, leaving populations more vulnerable to the newly evolved virus.