Figure 1. Some general concepts of virus evolution. (a) Genomic sequence alignments of related viruses often show conservation of functional domains (blocks) although they may vary in size, nucleotide sequence, relative position or orientation (block depicted by an arrow in the last two genomes). Sequence alignments of related viral genomes are the first data sets to be used for phylogenetic analyses. (b) Viral genomic sequences can be related by phylogenetic trees. Branches represent minimal genetic distances (nucleotide differences) among the different isolates. Clusters of related viruses are often referred to as clades, types or subtypes. Each tip of a branch is represented by a cloud to indicate the multiple variants that are often found in each viral isolate. Clouds are generally larger for RNA viruses than for complex DNA viruses. Deviant representatives of a distant cloud (arrow) may originate a new virus group that will undergo further diversification.

Figure 2. Mutation rates and frequencies. Cellular DNA replication is several orders of magnitude more accurate than RNA virus genome replication or retrotranscription. An average mutation rate of 10^–4 means that one misincorporation error at a given nucleotide template will occur once every 10 000 times that the polymerase copies this specific nucleotide. For both cellular DNA and viral RNA, mutation rates and frequencies much higher than average have been described (hypermutability). For RNA genomes mutation rates and frequencies lower than average may also occur (hypomutability). For specific studies on mutation rates and frequencies see the References and Further Reading. Terms are defined in Table 2.

Figure 3. Viral quasispecies. Horizontal lines represent genomes and symbols on lines represent different types of mutations. A selection event (or a transmission bottleneck; that is, a single genome is the origin of next distribution) leads to a change in the average sequence (small arrow, right). The average sequence is also termed the consensus sequence, and it is the one that includes at any position the nucleotide found most frequently in that position of the sequence distribution. Sequence distribution is also termed the mutant spectrum of the quasispecies. The virus population size that is transmitted (different sizes of the shaded large arrows) has an important influence in RNA virus evolution (see text).

Figure 4. Genetic shift and drift. Two forms of a virus consisting of a genome with eight segments, depicted in black or white, can form a reassortant made of different numbers of black and white segments when the two virus forms coinfect the same cell. The event that leads to the reassortment is genetic shift. When the reassorted (white) segments encode different antigenically relevant proteins the phenomenon is termed antigenic shift. Further evolution through point mutations (depicted as different symbols on the white segments) is termed genetic or antigenic drift.