Bosi et al. BMC Genomics 2011, 12:403 http://www.biomedcentral.com/1471-2164/12/403 R E S E A R C H A R T I C L E Open Access The mosaicism of plasmids revealed by atypical genes detection and analysis Emanuele Bosi, Renato Fani and Marco Fondi* Abstract Background: From an evolutionary viewpoint, prokaryotic genomes are extremely plastic and dynamic, since large amounts of genetic material are continuously added and/or lost through promiscuous gene exchange. In this picture, plasmids play a key role, since they can be transferred between different cells and, through genetic rearrangement(s), undergo gene(s) load, leading, in turn, to the appearance of important metabolic innovations that might be relevant for cell life. Despite their central position in bacterial evolution, a massive analysis of newly acquired functional blocks [likely the result of horizontal gene transfer (HGT) events] residing on plasmids is still missing. Results: We have developed a computational, composition-based, pipeline to scan almost 2000 plasmids for genes that differ significantly from their hosting molecule. Plasmids atypical genes (PAGs) were about 6% of the total plasmids ORFs and, on average, each plasmid possessed 4.4 atypical genes. Nevertheless, conjugative plasmids were shown to possess an amount of atypical genes than that found in not mobilizable plasmids, providing strong support for the central role suggested for conjugative plasmids in the context of HGT. Part of the retrieved PAGs are organized into (mainly short) clusters and are involved in important biological processes (detoxification, antibiotic resistance, virulence), revealing the importance of HGT in the spreading of metabolic pathways within the whole microbial community. Lastly, our analysis revealed that PAGs mainly derive from other plasmid (rather than coming from phages and/or chromosomes), suggesting that plasmid-plasmid DNA exchange might be the primary source of metabolic innovations in this class of mobile genetic elements. Conclusions: In this work we have performed the first large scale analysis of atypical genes that reside on plasmid molecules to date. Our findings on PAGs function, organization, distribution and spreading reveal the importance of plasmids-mediated HGT within the complex bacterial evolutionary network and in the dissemination of important biological traits. Background Comparative whole-genome analyses have demonstrated that horizontal gene transfer (HGT) provides a signifi- cant contribution to prokaryotic genome evolution/ innovation. In fact, it is very likely that a significant pro- portion of the genetic diversity exhibited by extant bac- teria might be the result of the acquisition of sequences from more or less distantly related organisms [1]. Indeed, HGT gives a venue for bacterial diversification by the reassortment of existing capabilities [1] and this formidable sexual promiscuity has given bacteria a great advantage, providing an awesome mechanism for * Correspondence: marco.fondi@unifi.it Lab. of Microbial and Molecular Evolution, Dept. of Evolutionary Biology, Via Romana 17-19, University of Florence, Italy ongoing adaptive evolution, a sort of permanently and rapidly evolving communal genome [2]. During evolution, HGT and recombination have shaped bacterial genomes, which today appear as com- plex mosaics of genes from different lineages, species, and genera [2]. In this picture, plasmids (collections of functional genetic modules that are organized into a stable, self- replicating entity or ‘replicon’), might have played (and might still play) a major role because they can be trans- ferred between microorganisms, thus representing nat- ural vectors for the transfer of genes and the functions they code for [3]. Moreover, it can be suggested that, during their evolutionary history, plasmids can undergo genetic rearrangements with either plasmids and/or © 2011 Bosi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.