Review
Selfish operons: the evolutionary impact of gene clustering in prokaryotes and eukaryotes

https://doi.org/10.1016/S0959-437X(99)00025-8Get rights and content

Abstract

The Selfish Operon Model postulates that the organization of bacterial genes into operons is beneficial to the constituent genes in that proximity allows horizontal cotransfer of all genes required for a selectable phenotype; eukaryotic operons formed for very different reasons. Horizontal transfer of selfish operons most probably promotes bacterial diversification.

Introduction

Nonrandom associations of genes contributing to single functions or phenotypes were observed when the first genetic maps were constructed. Some of these gene clusters were observed in eukaryotes, as affecting Drosophila morphology 1, 2, or biosynthetic pathways in Aspergillus [3] or Neurospora [4]. Clusters of functionally-related genes, however, are unusual in eukaryotes and many clusters were actually alleles of the same locus (eukaryotic operons are discussed further below).

In contrast, gene clusters were found to be the rule rather than the exception in bacterial taxa. The genes required for biosynthesis of many amino acids and cofactors, as well as those for degradation of sugars (e.g. arabinose, galactose or lactose) were clustered on the Escherichia coli and Salmonella enterica chromosomes [5]; gene clusters filled 40% of the first genetic map of Salmonella typhimurium [6]. A cogent hypothesis for the origin, maintenance and evolutionary role of gene clusters should predict the composition, distribution, and abundance of gene clusters in Bacteria and Archaea, as well as the dearth of gene clusters in Eukaryotes.

The Selfish Operon Model provides an extensible framework for understanding operon formation, persistence, and distribution among organisms; the organization of eukaryotic operons is discussed in this context.

Section snippets

Why are genes clustered?

Models for explaining why genes are clustered fall into five classes — four of which have been reviewed extensively [7]: the Natal Model, the Fisher Model, the Molarity Model, the Coregulation Model, and the Selfish Operon Model. Although each model may be invoked to explain aspects of the origin or maintenance of some operons, the Selfish Operon Model provides the most comprehensive framework for understanding the origin and persistence of Bacterial operons, and their near absence from the

Gene organization may be selfish, even if gene function is not

Consider addiction modules which, like the phd/doc system of bacteriophage P1 [14] (prevents host death/death on curing), encode a long-lived toxin (e.g. Doc) and a short-lived antidote (Phd). Should these genes be lost from a cell, the toxin will outlive its antidote and the cell will not persist; in this way, cells are addicted to the presence of the antidote. Proximity of the toxin- and antidote-encoding genes is selfish in that it allows for effective cotransfer into naı̈ve genomes —

Impact of selfish operons on bacterial evolution

The selfish operon allows genes to escape evolutionary elimination by invasion of new genomes — this that advantage can apply to operons conferring more ‘traditional’ metabolic functions too. In contrast to the systems described above, many bacterial operons confer highly beneficial functions that may be of long-term use to their new hosts: such functions include the biosynthesis of amino-acids, cofactors or other metabolites, the degradation of compounds as carbon or nitrogen sources, or the

Operons in eukaryotes

Although operons are ubiquitous and plentiful among prokaryotes, they are relatively rare among eukaryotes. Rare cases of apparent ribosome reinitiation [39] allow for a translation of dicistronic messages — such as those for growth/differentiation factor-1 [40]. Models of eukaryotic translation initiation, however, suggest that this phenomenon should be rare [41]. Selfish operons in bacteria can propagate easily because a promoter at the site of insertion allows transcription of all genes

Operons in Caenorhabditis elegans

Successful expression of polycistronic messages is evident in the nematode Caenorhabditis elegans 44••, 45. This feat is accomplished by using two different trans-splicing mechanisms [46], one of which is depicted in Figure 2. The SL-1 leader is trans-spliced to the generate the first mRNA from a polycistronic pre-RNA and the SL-2 leader is trans-spliced at internal receptor sites during maturation of mRNAs for downstream genes. Operons are not a rarity in C. elegans: recent genomic analyses

Different processes yield operons in bacteria and in eukaryotes

The Selfish Operon Model does not explain satisfactorily the existence or persistence of operons in C. elegans. Successful horizontal transfer of these operons is unlikely because a trans-splicing mechanism would be required for efficient expression in a recipient genome, and this machinery does not appear to be very widespread. Therefore, the formation of trans-spliced operons would serve to reduce the likelihood of successful horizontal transfer (Figure 3). Prior to operon formation,

Conclusions

Although operons are evident in both prokaryotic and eukaryotic lineages, the selective forces leading to their creation, as well as their impact in the diversification of lineages, is most likely distinctly different. Whereas most bacterial operons represent promiscuous packages of DNA that can confer novel metabolic functions to naı̈ve hosts after horizontal transfer, operons in C. elegans are very unlikely to move among genomes and may not confer any advantageous.

Acknowledgements

This work was supported by grants from the Alfred P Sloan Foundation and the David and Lucile Packard Foundation.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

References (49)

  • T. Komai

    Semi-allelic genes

    Amer Natur

    (1950)
  • E.B. Lewis

    Pseudoallelism in Drosophila melanogaster

    Genetics

    (1947)
  • W.R. Barratt et al.

    Map construction in Neurospora crassa

    Adv Genet

    (1954)
  • M. Demerec et al.

    Complex loci in microorganisms

    Annu Rev Microbiol

    (1959)
  • K.E. Sanderson et al.

    The linkage map of Salmonella typhimurium

    Genetics

    (1965)
  • J.G. Lawrence et al.

    Selfish operons: horizontal transfer may drive the evolution of gene clusters

    Genetics

    (1996)
  • C.A. Orengo et al.

    Identification and classification of protein fold families

    Protein Eng

    (1993)
  • R.A. Fisher

    The Genetical Theory of Natural Selection

    (1930)
  • F.W. Stahl et al.

    The evolution of gene clusters and genetic circularity in microorganisms

    Genetics

    (1966)
  • R. Losick et al.

    Changing views on the nature of the bacterial cell: from biochemistry to cytology

    J Bacteriol

    (1999)
  • T. Itoh et al.

    Evolutionary instability of operon structures disclosed by sequence comparisons of complete microbial genomes

    Mol Biol Evol

    (1999)
  • F. Jacob et al.

    L’opéron: groupe de gènes à expression coordonée par un opérateur

    C R Acad Sci III

    (1960)
  • A.S.G. Smith et al.

    The poison-antidote stability system of the broad-host-range Thiobacillus ferrooxidans plasmid pTF-FC2

    Mol Microbiol

    (1997)
  • E. Aizenman et al.

    An Escherichia coli chromosomal ‘addiction module’ regulated by guanosine 3′,5′-bispyrophosphate: a model for programmed bacterial cell death

    Proc Natl Acad Sci USA

    (1996)
  • Cited by (0)

    View full text