ReviewSelfish operons: the evolutionary impact of gene clustering in prokaryotes and eukaryotes
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)
An eight-chromosome map of Aspergillus nidulans
Adv Genet
(1958)- et al.
Plasmid addiction genes of bacteriophage P1: doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained
J Mol Biol
(1993) - et al.
The entericidin locus of Escherichia coli and its implications for programmed bacterial cell death
J Mol Biol
(1998) Selfishness and death: raison d’etre of restriction, recombination and mitochondria
Trends Genet
(1998)Selfish operons and speciation by gene transfer
Trends Microbiol
(1997)- et al.
How Salmonella became a pathogen
Trends Microbiol
(1997) - et al.
Evidence for a fourteen-gene, phnC to phnP locus for phosphonate metabolism in Escherichia coli
Gene
(1993) Trans-splicing and polycistronic transcription in Caenorhabditis elegans
Trends Genet
(1995)- et al.
Gene structure and organization in Caenorhabditis elegans
Curr Opin Genet Dev
(1996) - et al.
Gene linkage and steady state RNAs suggest trans-splicing may be associated with a polycistronic transcript in Schistosoma mansoni
Mol Biochem Parisitol
(1997)