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  • Review Article
  • Published:

The evolutionary conundrum of pathogen mimicry

Nature Reviews Microbiology volume 7, pages 787–797 (2009)Cite this article

Key Points

  • A wide range of pathogens use the strategy of mimicking host factors to gain selective advantages at host–pathogen interfaces.

  • Pathogen-encoded mimics can arise by horizontal gene transfer and divergence or independently, by convergent evolution. Some mimics mirror host functions (known as perfect mimicry), whereas others perform different functions (known as imperfect mimicry) to subvert host cellular processes.

  • Mimics impinge on key cellular processes, including the cell cycle, apoptosis, cytoskeletal dynamics, membrane traffic and immunity.

  • Mimicry presents a conundrum to host systems, which must discriminate self from mimics, and also to pathogens, which pay a fitness cost to deploy mimics. Similar trade-offs can influence the evolution of mimicry in ecological settings (for example, insect mimics).

  • Hosts can evolve to counteract mimicry in molecular arms races of adaptations. For example, the antiviral protein kinase R, which is the target of virus-encoded substrate mimics, has a highly flexible interaction interface and adapts on multiple surfaces to disfavour mimics.

  • The extent to which highly conserved cellular factors evolve to counteract mimics is an open question. Several routes seem to be available, including gene duplications followed by functional diversification.

Abstract

Evolutionary conflicts involving mimicry are found throughout nature. Diverse pathogens produce a range of 'mimics' that resemble host components in both form and function. Such mimics subvert crucial cellular processes, including the cell cycle, apoptosis, cytoskeletal dynamics and immunity. Here, we review the mounting evidence that mimicry of host processes is a highly successful strategy for pathogens. Discriminating mimics can be crucial for host survival, and host factors exist that effectively counteract mimics, using strategies that combine rapid evolution and an unexpected degree of flexibility in protein–protein interactions. Even in these instances, mimicry may alter the evolutionary course of fundamental cellular processes in host organisms.

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Figure 1: The evolutionary origins of mimics encoded by pathogens.
Figure 2: Mimics commandeer the cell.
Figure 3: Mimicry rings in ecological and molecular settings.
Figure 4: Mimics interfere with immunity factors.
Figure 5: PKR versusK3L: evolution of a host factor to defeat a mimic.

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Acknowledgements

We thank E. Goley, J. Kerns and A. Mercer for comments and suggestions and P. Wilkins for providing the images of insect mimics. We are supported by a Burroughs Wellcome Investigator in Pathogenesis Award and a National Science Foundation CAREER grant (H.S.M.), as well as an Ellison Medical Foundation Fellowship of the Life Sciences Research Foundation (N.C.E.). H.S.M. is a Howard Hughes Medical Institute early career scientist.

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  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, 98109, Washington, USA

    Nels C. Elde & Harmit S. Malik

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  1. Nels C. Elde
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  2. Harmit S. Malik
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Correspondence to Nels C. Elde.

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Glossary

Divergent evolution

The appearance of increasing differences in features between different lineages.

Convergent evolution

Independent acquisition of similar features in different lineages.

Perfect mimic

A pathogen factor that takes on the exact characteristics of a host factor and confers an advantage to the pathogen from the resemblance.

Fitness

The replicative or reproductive success of an entity.

Imperfect mimic

A pathogen factor with some characteristics of a host factor but also one or more distinct functions that confer additional advantages to the pathogen.

Adaptation

A feature that becomes prevalent in a population because of a selective advantage that it conveys.

Natural selection

The differential survival or reproduction of classes of entities that differ by one or more characteristics.

SNARE protein

Soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein (SNAP) receptor protein.

Positive selection

Selection for an allele that increases fitness.

Duplication

Production of another copy of a gene (or other sequence), which is incorporated into the genome and inherited.

Neofunctionalization

Divergence of duplicate genes such that one copy acquires a new function.

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Elde, N., Malik, H. The evolutionary conundrum of pathogen mimicry. Nat Rev Microbiol 7, 787–797 (2009). https://doi.org/10.1038/nrmicro2222

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