The genome sequence of an RNA virus population clusters around a consensus or average sequence, but each genome is different. A rare genome with a particular mutation may survive a selection event, and the mutation will then be found in all progeny genomes. The selection process is illustrated in this diagram:
The diagram on the left shows a small subset of the viral genomes that are present in a virus stock. Genomes are indicated by lines, and mutations are shown by different symbols. The consensus sequence for this population is shown as a line at the bottom. There are no mutations in the consensus sequence, even though every viral genome contains mutations. One of these genomes, indicated by the arrow, is able to survive a selection event (also called a genetic bottleneck), such as passage to a new host. This virus multiplies in the host and a new population of viruses emerges, shown by the diagram on the right. The consensus sequence for this population indicates that three mutations selected to survive the bottleneck are found in every member of the population. Error-prone replication ensures that the members of the new population have many other mutations in their genomes.
The type of population selection illustrated above most likely took place during the emergence of the new influenza H1N1 virus that is currently circulating globally. Imagine that the upper left diagram represents the sequences of one viral RNA segment of an influenza virus that is infecting a pig. The animal sneezes and several million viral particles are inhaled by a human who happens to be nearby. Of all the virions inhaled by the worker, only the one near the arrow can replicate efficiently in human cells. The three mutations are then present in that RNA segment of all the viruses that multiply in the human’s respiratory tract. Imagine similar selection events leading to a new population of viruses that are well adapted for transmission from person to person.
The quasispecies theory predicts that viruses are not just a collection of random mutants, but an interactive group of variants. Diversity of the population is critical for propagation of the viral infection. Recently it became experimentally feasible to test the idea that viral populations, not individual mutants, are the target of selection. We’ll examine those data next.