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3Fig. 2 a Phylogenetic tree of 287 sequenced bacterial genomes, based on aligments from the 16S rRNA gene sequence. The phyla are colour-coded; a more detailed view, with names of all the organisms can be found <strong>in</strong> the supplemental <strong>in</strong>formation: http:// www.cbs.dtu.dk/services/GenomeAtlas/suppl/FIG10yr/. b Photomicrograph show<strong>in</strong>g a dense fr<strong>in</strong>ge of anaerobic spirochaetes (B. pilosicoli) attached by one cell end to the lum<strong>in</strong>al surface of human colonic enterocytes, form<strong>in</strong>g a “false brush border”. Besides that of humans, B. pilosicoli colonises the large <strong>in</strong>test<strong>in</strong>e of a variety of mammals <strong>and</strong> birds, caus<strong>in</strong>g diarrhoea <strong>and</strong> reduced growth rates. Genomic sequence from B. pilosicoli is be<strong>in</strong>g analysed to assist <strong>in</strong> underst<strong>and</strong><strong>in</strong>g the genetic basis of this dense colonisation, <strong>in</strong>clud<strong>in</strong>g patterns of gene expression underly<strong>in</strong>g the complex <strong>in</strong>teractions that occur between <strong>in</strong>dividual bacterial cells <strong>and</strong> the colonised enterocytes. The photograph is courtesy of Dr. W. Bastiaan DeBoer, University of Western Australia, Perth, Western Australia they may be a part of mobile elements that are able to translocate <strong>and</strong> duplicate themselves. These could alternatively be non-functional ‘molecular fossils’ of previous <strong>in</strong>sertion events. F<strong>in</strong>ally, it could well be that these repeats serve some as yet undiscovered useful purpose. It is possible, for example, that repetitive sequences <strong>and</strong> <strong>in</strong>sertion sequence elements (ISs) contribute to genome plasticity through structural changes based on homologous recomb<strong>in</strong>ation (Kennedy et al. 2001; Fraser-Liggett 2005). A brief history of bacterial operons Much of the early classical work <strong>in</strong> microbiology has been done with E. coli, as this bacterium is relatively easy to culture <strong>in</strong> the laboratory. As more <strong>and</strong> more genetic <strong>in</strong>formation was gathered, it was considered a ‘typical’ bacterium, although E. coli is not more typical for bacteria than a rabbit is for all eukaryotic organisms. More than 40 years ago, a model was proposed for gene regulation of the catabolism of lactose <strong>in</strong> E. coli (Jacob et al. 1960; Jacob <strong>and</strong> Monod 1961). The model described an operon as a cluster of genes with related functions (encod<strong>in</strong>g, <strong>in</strong> this case, enzymes required for lactose degradation). This operon structure neatly allows regulation of gene expression by the concentration of lactose (Lewis et al. 1996; Reznikoff 1992). With the cont<strong>in</strong>uous expression of one small prote<strong>in</strong> (a repressor), wasteful expression of several other catabolic enzymes <strong>in</strong> the absence of lactose is prevented. S<strong>in</strong>ce the discovery of the lac operon, many more catabolic operons have been discovered, with positive <strong>and</strong> negative feedback strategies, <strong>and</strong> these illustrate the biological need to use resources as efficiently as possible. Many, if not all, bacterial genomes <strong>in</strong>deed display clusters of genes <strong>in</strong>volved <strong>in</strong> a s<strong>in</strong>gle process (be it co-jo<strong>in</strong>tly transcribed <strong>and</strong> regulated, as <strong>in</strong> classical operons, or with separate promoters <strong>and</strong> regulators), but the degree of operon gene organisation <strong>and</strong> gene cluster<strong>in</strong>g differs between species. In some bacteria, such as <strong>in</strong> Helicobacter pylori, operons are relatively unconserved, <strong>and</strong> genes <strong>in</strong>volved <strong>in</strong> one cellular process can be dispersed 169 throughout the genome (Tomb et al. 1997; Alm <strong>and</strong> Trust 1999), although more recent work suggest that perhaps there are more operons <strong>in</strong> H. pylori than previously thought (Price et al. 2005). There are currently many resources for prediction of operons (Rogoz<strong>in</strong> et al. 2004; Rosenfeld et al. 2004; Alm et al. 2005; Janga et al. 2005; Nishi et al. 2005; Price et al. 2005; Vallenet et al. 2006), <strong>in</strong>clud<strong>in</strong>g several databases, such as the Operon Database (Okuda et al. 2006), RegulonDB (Salgado et al. 2006a,b) <strong>and</strong> Gene- Chords (Zheng et al. 2005). How did the first operon evolve? There have been historically three models proposed for the orig<strong>in</strong>s of gene clusters. The first model, which dates back to 1945, proposed the cluster<strong>in</strong>g of genes to be the direct result of gene duplication <strong>and</strong> evolution (Horowitz 1945, 1965). Gene duplication can occur dur<strong>in</strong>g replication <strong>and</strong>, as a duplicated gene has more freedom to mutate, this is believed to be a classical mechanism for novel enzymes to evolve (Lazcano et al. 1995). However, although all genes with<strong>in</strong> an operon may be <strong>in</strong>volved <strong>in</strong> a s<strong>in</strong>gle metabolic process, their function <strong>and</strong> structure can vary considerably, <strong>and</strong> a phylogenic relationship between them is not always likely. The second model proposed for the evolution of operons is that coregulation of genes under a common promoter could provide selective advantage (Jacob et al. 1960). However, we now know that, <strong>in</strong> fact, it is possible to have coregulation of genes that are not physically l<strong>in</strong>ked together. Furthermore, this model does not really provide a gradual step-by-step mechanism for the evolution of operons. The third model for the evolution of an operon is that pre-exist<strong>in</strong>g genes moved together due to selective advantages of hav<strong>in</strong>g genes <strong>in</strong>volved <strong>in</strong> the same biochemical pathways or processes be<strong>in</strong>g physically close to each other. This hypothesis allows for structurally dist<strong>in</strong>ct genes to be part of one operon. This model requires both variation <strong>and</strong> frequent recomb<strong>in</strong>ation <strong>and</strong> has been proposed as an explanation of cluster<strong>in</strong>g of genes <strong>in</strong> bacteriophage genomes (Stahl <strong>and</strong> Murray 1966; Juhala et al. 2000). In addition to these three views, there are other alternatives. Gene cluster<strong>in</strong>g may be of selective advantage <strong>in</strong> the case of horizontal gene transfer (see section below) <strong>and</strong>, based on this idea, a fourth mechanism, ‘selfish operon’ model, was proposed (Lawrence <strong>and</strong> Roth 1996). This view has been recently called <strong>in</strong>to question, based on the physical cluster<strong>in</strong>g of essential genes <strong>in</strong> the E. coli K-12 genome (Pal <strong>and</strong> Hurst 2004). Two other alternatives for operon evolution deal with chromat<strong>in</strong> structure <strong>and</strong> the physical location of genes <strong>in</strong> bacterial chromosomes, where transcription <strong>and</strong> translation are coupled (Pal <strong>and</strong> Hurst 2004). It is quite possible that, <strong>in</strong> fact, there is no one “correct” mechanism, but perhaps different mechanisms are <strong>in</strong>volved at the same time. For example, the selective advantage of gene cluster<strong>in</strong>g dur<strong>in</strong>g horizontal gene transfer is exemplified by the cluster<strong>in</strong>g of multiple antibiotic
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BIBLIOGRAPHY J. Rogers, P. F. Stadl
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BIBLIOGRAPHY Q. Jin, Z. Yuan, J. Xu
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BIBLIOGRAPHY Velicer, F.-J. Vorholt