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The evolution of genetic regulatory systems in bacteria

Nature Reviews Genetics volume 5, pages 169–178 (2004)Cite this article

Key Points

  • The genomes of bacterial species show enormous plasticity in the function of individual genes, in genome organization and in regulatory organization.

  • Genes and parts of genes are moved within and between genomes, and contiguous pieces of DNA encoding many genes are moved about by mobile genetic elements. Overlaid on these genomic rearrangement processes is an inescapable rate of random point mutation.

  • By rapidly introducing new genes into existing genomes, horizontal gene transfer (HGT) circumvents the slow step of complete gene creation and accelerates genome innovation. About 18% of the E. coli genome seems to have been acquired by HGT, for example.

  • A 'modular' organization of cellular functions appears in spatial, temporal, chemical and genetic contexts. This modular structure arises spontaneously as a result of the fitness advantages of co-regulation, co-action, and the more efficient HGT of co-located genes that work together.

  • If one species in a stable community achieves a notable improvement in fitness through mutation or HGT, it will cause the wholesale reoptimization of the local biosphere. Such events are random, rare and unpredictable, but of wide significance when they do occur.

  • Useful foreign genes are integrated into a new host's regulatory system by the processes of 'experimental' genome reorganization (that is, by point mutations and shuffling segments of DNA) that occur at a persistent, but random rate. Experiments with cells lacking an essential metabolic pathway, but containing a promoterless rescue operon, have shown that mutations in the upstream operator region can readily generate active promoter sites to create viable mutant strains.

  • Bacterial 'species' are ecotypes, the core identity of which is preserved by selective pressures that maintain each organism's particular complement of enzymes, pathways, morphological structures, sensors, signalling networks and decision logic circuits that together enable and implement its survival strategy in a target niche.

  • By exploiting the natural adaptive processes of evolutionary mutation and selection we might be able to engineer bacteria with novel circuitry that directs new types of responses to external signals.

Abstract

The genomes of bacterial species show enormous plasticity in the function of individual genes, in genome organization and in regulatory organization. Over millions of years, both bacterial genes and their genomes have been extensively reorganized and adapted so that bacteria occupy virtually every environmental niche on the earth. In addition, changes have occurred in the regulatory circuitry that controls cell operations, cell-cycle progression and responses to environmental signals. The mechanisms that underlie the adaptation of the bacterial regulatory circuitry are crucial for understanding the bacterial biosphere and have important roles in the emergence of antibiotic resistance.

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Figure 1: Example of a bacterial regulatory circuit.
Figure 2: Flagella organization in Caulobacter, Vibrio and Salmonella.

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Acknowledgements

H.H.M. is supported by the Office of Science of the U.S. Department of Energy (DOE), by the Office of Naval Research and by the DARPA Defense Sciences Office. B.S. is supported by a National Defense Science and Engineering fellowship from the Army Research Office. A.P.A. is supported by the Office of Science of the U.S. DOE, the DARPA Information Processing Technology Office and by the Howard Hughes Medical Institute. We thank L. Shapiro and R. Losick for helpful comments on the manuscript.

Author information

Authors and Affiliations

  1. Department of Developmental Biology, Stanford University School of Medicine, B300 Beckman Center, Stanford, 94305, California, USA

    Harley H. McAdams & Balaji Srinivasan

  2. Physical Bioscience Division, Department of Bioengineering, Lawrence Berkeley Laboratories, University of California at Berkeley, and the Howard Hughes Medical Institute, Berkeley, 94720, California, USA

    Adam P. Arkin

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Correspondence to Harley H. McAdams.

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Glossary

REGULATORY CIRCUIT

A reaction network that can involve transcription factors, promoters, enzymes, structural genes, functional RNAs and metabolites. Regulatory networks control activation of genes in development, in the cell cycle and in the activation of metabolic pathways.

FUNCTIONAL GENOMICS

The use of genome-wide or system-wide experimental approaches to assess gene function. It also refers to the analysis of gene function within the context of the overall design and behaviour of the organism.

CIRCUIT MOTIFS

Elements of circuit organization that are found repeatedly in regulatory circuits of different organisms and even in different regulatory subcircuits in the same organism.

TWO-COMPONENT SYSTEMS

Signal-transduction systems that enable bacteria to regulate cellular functions in response to changing environmental conditions. They are composed of a histidine kinase sensor protein and a response regulator that frequently acts as a transcription factor.

KINETIC PARAMETERS

The rate constants of chemical reactions that describe how fast the reaction takes place.

ARCHAEBACTERIA

An ancient kingdom of unicellular microorganisms that are phylogenetically distinct from bacteria and eukaryotes. They are often found in extreme environments, such as near deep-sea vents.

XENOBIOTIC

A compound that is foreign to biological systems, often referring to human-made compounds that are resistant to biodegradation.

TRYPTOPHAN OPERON

The group of genes that control the biosynthesis of tryptophan.

ENDOSYMBIONT

An organism that grows inside another organism. The relationship can be either mutualistic (both species benefit) or commensalistic (one species benefits, whereas the other is not affected).

HORIZONTAL GENE TRANSFER

The transfer of genetic material among cells that belong to different strains, species or genera.

INTEGRON

A genetic unit that, among others, encodes proteins that splice gene cassettes into chromosomes, where the cassettes can become functional.

CONJUGATIVE TRANSPOSONS

Discrete DNA elements that can transfer themselves from donor to recipient while the two are in direct physical contact. Their broad host range makes them important in horizontal transfer and bacterial evolution.

EVOLVABILITY

The ability of random genetic variation to produce phenotypic changes that can increase fitness (intrinsic evolvability) or the ability of a population to respond to selection (extrinsic evolvability).

16S rRNA GENES

Genes that are transcribed into the 16S rRNA molecule, a major component of the bacterial small ribosomal subunit. The strong sequence conservation of this molecule makes it ideal for detecting large evolutionary distances between two organisms.

GENE CASSETTES

Small mobile DNA elements that typically consist of a promoterless open reading frame and a recombination site. Gene cassettes are ubiquitous in environmental DNA samples.

α-PROTEOBACTERIA

A class of primarily oligotrophic bacteria within the proteobacteria that have high morphological and ecological diversity.

METHYLTRANSFERASE

An enzyme that catalyses the addition of a methyl group, often to adenine or cytosine molecules in DNA.

σ54 TRANSCRIPTIONAL ACTIVATOR

Sigma factors are variable protein components of the bacterial RNA polymerase that have great influence on where the polymerase binds to DNA. The ability of σ54, in particular, to initiate transcription by the polymerase might be affected by activators that bind at distant sites on the DNA.

CONVERGENT EVOLUTION

Two items are said to be the result of convergent evolution if their similarities arose by independent processes without common ancestry. This usually reflects evolutionary adaptation to similar environmental conditions.

HEAT-SHOCK RESPONSE

A mechanism that involves activation of many genes that cells use to maintain stability when subjected to thermal stress.

LYSOGENIC STATE

A phage integrated into a bacterial cell's chromosome is, in a latent form, called a 'lysogenic state'. Environmental stress can cause the lysogenic phage to leave the chromosome and produce infectious phage particles followed by bursting of the host cell.

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McAdams, H., Srinivasan, B. & Arkin, A. The evolution of genetic regulatory systems in bacteria. Nat Rev Genet 5, 169–178 (2004). https://doi.org/10.1038/nrg1292

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