Resistance pathways

We know virus develop resistance to drugs. The interesting cases are when resistance depends on combinations of mutations; mutational pathways.

The concept pathway implies an order. Is there one?
fitness landscapse or seascape?
survival of the fittest or the flattest?
colonizer/competitor dynamics?

What is a reference sequence? Does this define the virus???

Possible titles "Tracing evolutionary pathways through seascapes and bottlenecks"

hmmm-- ship in a bottle, early mariners, exploring, setting up trade outposts???