Review
Why Might Bacterial Pathogens Have Small Genomes?

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Bacteria that cause serious disease often have smaller genomes, and fewer genes, than their nonpathogenic, or less pathogenic relatives. Here, we review evidence for the generality of this association, and summarise the various reasons why the association might hold. We focus on the population genetic processes that might lead to reductive genome evolution, and show how several of these could be connected to pathogenicity. We find some evidence for most of the processes having acted in bacterial pathogens, including several different modes of genome reduction acting in the same lineage. We argue that predictable processes of genome evolution might not reflect any common underlying process.

Section snippets

Reductive Genome Evolution and Pathogenicity (RGEP)

Bacterial pathogens (see Glossary) are one of the most serious threats to human health worldwide, and are evolving resistance to antibiotics at an alarming rate [1]. In a postantibiotic era creative approaches to combating infectious disease will become paramount.

One crucial research goal is to understand why and how bacteria become pathogens. Of course, every instance of pathogen emergence is unique in some way, and they could have little in common. But if we were able to identify any common

Cause, Consequence or Correlate?

One obvious question about RGEP is how or whether the association is causal. At first glance, the comparative evidence argues against a causal relationship. This is because the clearest and best-known examples of bacterial genome reduction include non-pathogens, such as the free-living marine bacteria Pelagibacter and Prochlorococcus 16, 17 and mutualist endosymbionts, such as Buchnera and Portiera 18, 19, 20. Furthermore, the symbionts have a host-restricted and intracellular ecology that is

The Population Genetics of Genome Reduction

A distinct approach to understanding RGEP is to consider the population genetic processes that might lead to bacterial genome reduction (Table 1). This arrangement allows us to draw connections to other examples of reductive genome evolution 3, 20, 37. Here, we ask whether any of the processes has a consistent association with pathogenicity, whether as cause, consequence or correlate.

Concluding Remarks

This article has reviewed the possible association between reductive genome evolution and bacterial pathogenicity (RGEP). One major conclusion is how little we know about this association. Major questions remain about its generality, and how, if at all, the association is causal (see Outstanding Questions).

We have arranged this review according to a third consideration: the population genetic processes that might be involved in genome reduction.

This arrangement cuts across the factors that are

Acknowledgements

We are very grateful to Jane Charlesworth, Eric Miller, Laurence Hurst, and two anonymous reviewers for their helpful suggestions. LW is supported by a Dorothy Hodgkin Fellowship funded by the Royal Society (Grant Number DH140195) and a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 109385/Z/15/Z).

Glossary

Antivirulence gene
in the narrow sense, a region of genome that functions to suppress the operation of a virulence gene. More broadly, any region whose removal or inactivation increases virulence.
Arms race
evolution of adaptations and counteradaptations during antagonistic coevolution (see also Red Queen).
Auxotrophic
unable to synthesise a compound required for growth.
dN/dS
in protein-coding sequences, the rate of substitutions that change the amino acid, divided by the rate of synonymous changes

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