# Bacteriophage experimental evolution

Experimental evolution studies are a means of testing evolutionary theory under carefully designed, reproducible experiments. Given enough time, space, and money, any organism could be used for experimental evolution studies. However, those with rapid generation times, high mutation rates, large population sizes, and small sizes increase the feasibility of experimental studies in a laboratory context. For these reasons, bacteriophages (i.e. viruses that infect bacteria) are especially favored by experimental evolutionary biologists. Bacteriophages, and microbial organisms, can be frozen in stasis, facilitating comparison of evolved strains to ancestors. Additionally, microbes are especially labile from a molecular biologic perspective. Many molecular tools have been developed to manipulate the genetic material of microbial organisms, and because of their small genome sizes, sequencing the full genomes of evolved strains is trivial. Therefore, comparisons can be made for the exact molecular changes in evolved strains during adaptation to novel conditions.

## Experimental studies, by category
### Laboratory phylogenetics

Phylogenetics is the study of the evolutionary relatedness of organisms. Laboratory phylogenetics is the study of the evolutionary relatedness of laboratory-evolved organisms. An advantage of laboratory phylogenetics is the exact evolutionary history of an organism is known, rather than estimated as is the case for most organisms.

### Epistasis

Epistasis is the dependence of the effect of one gene or mutation on the presence of another gene or mutation. Theoretically epistasis can be of three forms: no epistasis (additive inheritance), synergistic (or positive) epistasis and antagonistic (or negative) epistasis. In synergistic epistasis, each additional mutation has increasing negative impact on fitness. In antagonistic epistasis, the effect of each mutation declines with increasing numbers of mutation. Understanding whether the majority of genetic interactions are synergistic or antagonistic will help solve such problems as the evolution of sex.
The phage literature provides many examples of epistasis which are not studied under the context of experimental evolution nor necessarily described as examples of epistasis.

### Experimental adaptation

Experimental adaptation involves selection of organisms either for specific traits or under specific conditions. For example, strains could be evolved under conditions of high temperatures to observe the molecular changes that facilitate survival and reproduction under those conditions.
The reader should be aware that numerous phage experimental adaptations were performed in the early decades of phage study.

#### Adaptation to new or modified hosts.

The older phage literature, e.g., pre-1950s, contains numerous examples of phage adaptations to different hosts.

#### Adaptation to modified conditions

The older phage literature, e.g., pre-1950s, also contains examples of phage adaptations to different culture conditions, such as phage T2 adaptation to low salt conditions.

#### Adaptation as compensation for deleterious mutations.

There are many examples in early phage literature of bacteriophages adapting and compensating for deleterious mutations.

#### Adaptation as toward change in phage virulence

Virulence is the negative impact that a pathogen (or parasite) has on the Darwinian fitness of a harboring organism (host). For phage, virulence results either in reduction of bacterial division rates or, more typically, in the death (via lysis) of individual bacteria. A number of theory papers exist on this subject, especially as it applies to the evolution of phage latent period.
The older phage literature contains numerous references to phage virulence, and phage virulence evolution. However, the reader should be warned that virulence is often used as a synonym for "not temperature", a usage which is neither employed here nor to be encouraged generally.

### Impact of sex/coinfection

More than one phage can coinfect the same bacterial cell. When this happens, the phage can exchange genes, which is equivalent to "sex." Note that a number of the immediately following studies employ sex to overcome Muller's ratchet while papers that demonstrate Muller's ratchet (i.e., without employing sex to overcome the result) are instead presented under that heading.

### Muller’s ratchet

Muller’s ratchet is the gradual, but irreversible accumulation of deleterious mutations in asexual organisms. Asexual organisms do not undergo gene exchange and therefore cannot recreate mutation-free genomes. Chao, 1997, provides a phage-emphasizing review of the subject.

### Prisoner’s dilemma

Prisoner's dilemma is a part of game theory which involves two individuals choosing to cooperate or defect, reaping differential rewards. During phage coinfection, it pertains to viruses which produce more protein products than they use (cooperators) and viruses which use more protein products than they produce (defectors).

### Coevolution

Coevolution is the study of the evolutionary influence that two species have upon each other. Phage-bacterial coevolution is typically studied within the context of phage community ecology.