Sequence analysis of tyrosine recombinases allows annotation of mobile genetic elements in prokaryotic genomes.
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ABSTRACT:
SUBMITTER: Smyshlyaev G
PROVIDER: S-EPMC8138268 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTyrosine-based site-specific recombinases (TBSSRs) are DNA breaking-rejoining enzymes. In bacterial genomes, they play a major role in the comings and goings of mobile genetic elements (MGEs), such as temperate phage genomes, integrated conjugative elements (ICEs) or integron cassettes. TBSSRs are also involved in the segregation of plasmids and chromosomes, the resolution of plasmid dimers and of co-integrates resulting from the replicative transposition of transposons. With the aim of improving the annotation of TBSSR genes in genomic sequences and databases, which so far is far from robust, we built a set of over 1,300 TBSSR protein sequences tagged with their genome of origin. We organized them in families to investigate: i) whether TBSSRs tend to be more conserved within than between classes of MGE types and ii) whether the (sub)families may help in understanding more about the function of TBSSRs associated in tandem or trios on plasmids and chromosomes.ResultsA total of 67% of the TBSSRs in our set are MGE type specific. We define a new class of actinobacterial transposons, related to Tn554, containing one abnormally long TBSSR and one of typical size, and we further characterize numerous TBSSRs trios present in plasmids and chromosomes of α- and β-proteobacteria.ConclusionsThe simple in silico procedure described here, which uses a set of reference TBSSRs from defined MGE types, could contribute to greatly improve the annotation of tyrosine-based site-specific recombinases in plasmid, (pro)phage and other integrated MGE genomes. It also reveals TBSSRs families whose distribution among bacterial taxa suggests they mediate lateral gene transfer.
| S-EPMC3414803 | biostudies-literature
Project description:MotivationDetailed and accurate analysis of mobile genetic elements (MGEs) in bacteria is essential to deal with the current threat of multiresistant microbes. The overwhelming use of draft, contig-based genomes hinder the delineation of the genetic structure of these plastic and variable genomic stretches, as in the case of pipolins, a superfamily of MGEs that spans diverse integrative and plasmidic elements, characterized by the presence of a primer-independent DNA polymerase.ResultsExplorePipolin is a Python-based pipeline that screens for the presence of the element and performs its reconstruction and annotation. The pipeline can be used on virtually any genome from diverse organisms and of diverse quality, obtaining the highest-scored possible structure and reconstructed out of different contigs if necessary. Then, predicted pipolin boundaries and pipolin encoded genes are subsequently annotated using a custom database, returning the standard file formats suitable for comparative genomics of this mobile element.Availability and implementationAll code is available and can be accessed here: github.com/pipolinlab/ExplorePipolin.Supplementary informationSupplementary data are available at Bioinformatics Advances online.
| S-EPMC9710591 | biostudies-literature
Project description:BackgroundThe insertion sequence elements (IS elements) represent the smallest and the most abundant mobile elements in prokaryotic genomes. It has been shown that they play a significant role in genome organization and evolution. To better understand their function in the host genome, it is desirable to have an effective detection and annotation tool. This need becomes even more crucial when considering rapid-growing genomic and metagenomic data. The existing tools for IS elements detection and annotation are usually based on comparing sequence similarity with a database of known IS families. Thus, they have limited ability to discover distant and putative novel IS elements.ResultsIn this paper, we present digIS, a software tool based on profile hidden Markov models assembled from catalytic domains of transposases. It shows a very good performance in detecting known IS elements when tested on datasets with manually curated annotation. The main contribution of digIS is in its ability to detect distant and putative novel IS elements while maintaining a moderate level of false positives. In this category it outperforms existing tools, especially when tested on large datasets of archaeal and bacterial genomes.ConclusionWe provide digIS, a software tool using a novel approach based on manually curated profile hidden Markov models, which is able to detect distant and putative novel IS elements. Although digIS can find known IS elements as well, we expect it to be used primarily by scientists interested in finding novel IS elements. The tool is available at https://github.com/janka2012/digIS.
| S-EPMC8147514 | biostudies-literature
Project description:BACKGROUND:Recent advances in sequencing technology have allowed us to investigate personal genomes to find structural variations, which have been studied extensively to identify their association with the physiology of diseases such as cancer. In particular, mobile genetic elements (MGEs) are one of the major constituents of the human genomes, and cause genome instability by insertion, mutation, and rearrangement. RESULT:We have developed a new program, iMGEins, to identify such novel MGEs by using sequencing reads of individual genomes, and to explore the breakpoints with the supporting reads and MGEs detected. iMGEins is the first MGE detection program that integrates three algorithmic components: discordant read-pair mapping, split-read mapping, and insertion sequence assembly. Our evaluation results showed its outstanding performance in detecting novel MGEs from simulated genomes, as well as real personal genomes. In detail, the average recall and precision rates of iMGEins are 96.67 and 100%, respectively, which are the highest among the programs compared. In the testing with real human genomes of the NA12878 sample, iMGEins shows the highest accuracy in detecting MGEs within 20?bp proximity of the breakpoints annotated. CONCLUSION:In order to study the dynamics of MGEs in individual genomes, iMGEins was developed to accurately detect breakpoints and report inserted MGEs. Compared with other programs, iMGEins has valuable features of identifying novel MGEs and assembling the MGEs inserted.
| S-EPMC6299635 | biostudies-literature
Project description:BackgroundAccurate annotation of translation initiation sites (TISs) is essential for understanding the translation initiation mechanism. However, the reliability of TIS annotation in widely used databases such as RefSeq is uncertain due to the lack of experimental benchmarks.ResultsBased on a homogeneity assumption that gene translation-related signals are uniformly distributed across a genome, we have established a computational method for a large-scale quantitative assessment of the reliability of TIS annotations for any prokaryotic genome. The method consists of modeling a positional weight matrix (PWM) of aligned sequences around predicted TISs in terms of a linear combination of three elementary PWMs, one for true TIS and the two others for false TISs. The three elementary PWMs are obtained using a reference set with highly reliable TIS predictions. A generalized least square estimator determines the weighting of the true TIS in the observed PWM, from which the accuracy of the prediction is derived. The validity of the method and the extent of the limitation of the assumptions are explicitly addressed by testing on experimentally verified TISs with variable accuracy of the reference sets. The method is applied to estimate the accuracy of TIS annotations that are provided on public databases such as RefSeq and ProTISA and by programs such as EasyGene, GeneMarkS, Glimmer 3 and TiCo. It is shown that RefSeq's TIS prediction is significantly less accurate than two recent predictors, Tico and ProTISA. With convincing proofs, we show two general preferential biases in the RefSeq annotation, i.e. over-annotating the longest open reading frame (LORF) and under-annotating ATG start codon. Finally, we have established a new TIS database, SupTISA, based on the best prediction of all the predictors; SupTISA has achieved an average accuracy of 92% over all 532 complete genomes.ConclusionLarge-scale computational evaluation of TIS annotation has been achieved. A new TIS database much better than RefSeq has been constructed, and it provides a valuable resource for further TIS studies.
| S-EPMC2362131 | biostudies-literature
Project description:BackgroundProtein-coding gene detection in prokaryotic genomes is considered a much simpler problem than in intron-containing eukaryotic genomes. However there have been reports that prokaryotic gene finder programs have problems with small genes (either over-predicting or under-predicting). Therefore the question arises as to whether current genome annotations have systematically missing, small genes.ResultsWe have developed a high-performance computing methodology to investigate this problem. In this methodology we compare all ORFs larger than or equal to 33 aa from all fully-sequenced prokaryotic replicons. Based on that comparison, and using conservative criteria requiring a minimum taxonomic diversity between conserved ORFs in different genomes, we have discovered 1,153 candidate genes that are missing from current genome annotations. These missing genes are similar only to each other and do not have any strong similarity to gene sequences in public databases, with the implication that these ORFs belong to missing gene families. We also uncovered 38,895 intergenic ORFs, readily identified as putative genes by similarity to currently annotated genes (we call these absent annotations). The vast majority of the missing genes found are small (less than 100 aa). A comparison of select examples with GeneMark, EasyGene and Glimmer predictions yields evidence that some of these genes are escaping detection by these programs.ConclusionsProkaryotic gene finders and prokaryotic genome annotations require improvement for accurate prediction of small genes. The number of missing gene families found is likely a lower bound on the actual number, due to the conservative criteria used to determine whether an ORF corresponds to a real gene.
| S-EPMC3098052 | biostudies-literature
Project description:The roles of restriction-modification (R-M) systems in providing immunity against horizontal gene transfer (HGT) and in stabilizing mobile genetic elements (MGEs) have been much debated. However, few studies have precisely addressed the distribution of these systems in light of HGT, its mechanisms and its vectors. We analyzed the distribution of R-M systems in 2261 prokaryote genomes and found their frequency to be strongly dependent on the presence of MGEs, CRISPR-Cas systems, integrons and natural transformation. Yet R-M systems are rare in plasmids, in prophages and nearly absent from other phages. Their abundance depends on genome size for small genomes where it relates with HGT but saturates at two occurrences per genome. Chromosomal R-M systems might evolve under cycles of purifying and relaxed selection, where sequence conservation depends on the biochemical activity and complexity of the system and total gene loss is frequent. Surprisingly, analysis of 43 pan-genomes suggests that solitary R-M genes rarely arise from the degradation of R-M systems. Solitary genes are transferred by large MGEs, whereas complete systems are more frequently transferred autonomously or in small MGEs. Our results suggest means of testing the roles for R-M systems and their associations with MGEs.
| S-EPMC4176335 | biostudies-literature
Project description:Simple sequence repeats (SSRs) in DNA sequences are composed of tandem iterations of short oligonucleotides and may have functional and/or structural properties that distinguish them from general DNA sequences. They are variable in length because of slip-strand mutations and may also affect local structure of the DNA molecule or the encoded proteins. Long SSRs (LSSRs) are common in eukaryotes but rare in most prokaryotes. In pathogens, SSRs can enhance antigenic variance of the pathogen population in a strategy that counteracts the host immune response. We analyze representations of SSRs in >300 prokaryotic genomes and report significant differences among different prokaryotes as well as among different types of SSRs. LSSRs composed of short oligonucleotides (1-4 bp length, designated LSSR(1-4)) are often found in host-adapted pathogens with reduced genomes that are not known to readily survive in a natural environment outside the host. In contrast, LSSRs composed of longer oligonucleotides (5-11 bp length, designated LSSR(5-11)) are found mostly in nonpathogens and opportunistic pathogens with large genomes. Comparisons among SSRs of different lengths suggest that LSSR(1-4) are likely maintained by selection. This is consistent with the established role of some LSSR(1-4) in enhancing antigenic variance. By contrast, abundance of LSSR(5-11) in some genomes may reflect the SSRs' general tendency to expand rather than their specific role in the organisms' physiology. Differences among genomes in terms of SSR representations and their possible interpretations are discussed.
| S-EPMC1895974 | biostudies-literature
Project description:The integration of mobile genetic elements into their host chromosome influences the immediate fate of cellular organisms and gradually shapes their evolution. Site-specific recombinases catalyzing this integration have been extensively characterized both in bacteria and eukarya. More recently, a number of reports provided the in-depth characterization of archaeal tyrosine recombinases and highlighted new particular features not observed in the other two domains. In addition to being active in extreme environments, archaeal integrases catalyze reactions beyond site-specific recombination. Some of these integrases can catalyze low sequence specificity recombination reactions with the same outcome as homologous recombination events generating deep rearrangements of their host genome. A large proportion of archaeal integrases are termed suicidal due to the presence of a specific recombination target within their own gene. The paradoxical maintenance of integrases which disrupt their gene upon integration implies novel mechanisms for their evolution. In this review, we assess the diversity of the archaeal tyrosine recombinases using a phylogenomic analysis based on an exhaustive similarity network. We outline the biochemical, ecological and evolutionary properties of these enzymes in the context of the families we identified and emphasize similarities and differences between archaeal recombinases and their bacterial and eukaryal counterparts.
| S-EPMC8371274 | biostudies-literature
Project description:Coagulase negative staphylococci are normal inhabitant of the human skin flora that account for an increasing number of infections, particularly hospital-acquired infections. Staphylococcus lugdunensis has emerged as a most virulent species causing various infections with clinical characteristics close to what clinicians usually observe with Staphylococcus aureus and both bacteria share more than 70% of their genome. Virulence of S. aureus relies on a large repertoire of virulence factors, many of which are encoded on mobile genetic elements. S. lugdunensis also bears various putative virulence genes but only one complete genome with extensive analysis has been published with one prophage sequence (?SL2) and a unique plasmid was previously described. In this study, we performed de novo sequencing, whole genome assembly and annotation of seven strains of S. lugdunensis from VISLISI clinical trial. We searched for the presence of virulence genes and mobile genetics elements using bioinformatics tools. We identified four new prophages, named ?SL2 to ?SL4, belonging to the Siphoviridae class and five plasmids, named pVISLISI_1 to pVISLISI_5. Three plasmids are homologous to known plasmids that include, amongst others, one S. aureus plasmid. The two other plasmids were not described previously. This study provides a new context for the study of S. lugdunensis virulence suggesting the occurrence of several genetic recombination' with other staphylococci.
| S-EPMC5425232 | biostudies-literature