scholarly journals Genomic Stability and Genetic Defense Systems in Dolosigranulum pigrum a Candidate Beneficial Bacterium from the Human Microbiome

2021 ◽  
Author(s):  
Stephany Flores Ramos ◽  
Silvio D. Brugger ◽  
Isabel Fernández Escapa ◽  
Chelsey A Skeete ◽  
Sean L Cotton ◽  
...  
Keyword(s):  
Human Microbiome ◽  
Genomic Stability ◽  
Gene Clusters ◽  
Mobile Genetic Elements ◽  
Phylogenomic Analysis ◽  
Hotspot Analysis ◽  
Systematic Analysis ◽  
Chromosomal Structure ◽  
Genetic Elements ◽  
Defense Systems

Dolosigranulum pigrum is positively associated with indicators of health in multiple epidemiological studies of human nasal microbiota. Knowledge of the basic biology of D. pigrum is a prerequisite for evaluating its potential for future therapeutic use; however, such data are very limited. To gain insight into D. pigrum's chromosomal structure, pangenome and genomic stability, we compared the genomes of 28 D. pigrum strains that were collected across 20 years. Phylogenomic analysis showed closely related strains circulating over this period and closure of 19 genomes revealed highly conserved chromosomal synteny. Gene clusters involved in the mobilome and in defense against mobile genetic elements (MGEs) were enriched in the accessory genome versus the core genome. A systematic analysis for MGEs identified the first candidate D. pigrum prophage and insertion sequence. A systematic analysis for genetic elements that limit the spread of MGEs, including restriction modification (RM), CRISPR-Cas, and deity-named defense systems, revealed strain-level diversity in host defense systems that localized to specific genomic sites including one RM system hotspot. Analysis of CRISPR spacers pointed to a wealth of MGEs against which D. pigrum defends itself. These results reveal a role for horizontal gene transfer and mobile genetic elements in strain diversification while highlighting that in D. pigrum this occurs within the context of a highly stable chromosomal organization protected by a variety of defense mechanisms.

scholarly journals A Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics

Cell ◽  
2014 ◽  
Vol 158 (6) ◽  
pp. 1402-1414 ◽  
Author(s):  
Mohamed S. Donia ◽  
Peter Cimermancic ◽  
Christopher J. Schulze ◽  
Laura C. Wieland Brown ◽  
John Martin ◽  
...  
Keyword(s):  
Human Microbiome ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Systematic Analysis

scholarly journals Phylogenomics of the Maverick Virus-Like Mobile Genetic Elements of Vertebrates

2021 ◽  
Author(s):  
Jose Gabriel Nino Barreat ◽  
Aris Katzourakis
Keyword(s):  
Purifying Selection ◽  
Mobile Genetic Elements ◽  
Phylogenomic Analysis ◽  
Genetic Elements ◽  
Bayesian Phylogenetic Analysis ◽  
Viral Particles ◽  
Ancient Lineage ◽  
Viral Nature ◽  
Dsdna Viruses ◽  
New Evidence

Abstract Mavericks are virus-like mobile genetic elements found in the genomes of eukaryotes. Although Mavericks encode capsid morphogenesis homologs, their viral particles have not been observed. Here, we provide new evidence supporting the viral nature of Mavericks and the potential existence of virions. To this end, we conducted a phylogenomic analysis of Mavericks in hundreds of vertebrate genomes, discovering 134 elements with an intact coding capacity in 17 host species. We reveal an extensive genomic fossil record in 143 species and date three groups of elements to the Late Cretaceous. Bayesian phylogenetic analysis using genomic fossil orthologs suggests that Mavericks have infected osteichthyans for ∼419 My. They have undergone frequent cross-species transmissions in cyprinid fish and all core genes are subject to strong purifying selection. We conclude that vertebrate Mavericks form an ancient lineage of aquatic dsDNA viruses which are probably still functional in some vertebrate lineages.

scholarly journals Disentangling the effects of selection and loss bias on gene dynamics

2017 ◽  
Author(s):  
Jaime Iranzo ◽  
José A. Cuesta ◽  
Susanna Manrubia ◽  
Mikhail I. Katsnelson ◽  
Eugene V. Koonin
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Genome Size ◽  
Mobile Genetic Elements ◽  
Loss Ratio ◽  
Effective Population ◽  
Strong Selection ◽  
Genetic Elements ◽  
Defense Systems ◽  
Parasite Defense

ABSTRACTWe combine mathematical modelling of genome evolution with comparative analysis of prokaryotic genomes to estimate the relative contributions of selection and intrinsic loss bias to the evolution of different functional classes of genes and mobile genetic elements (MGE). An exact solution for the dynamics of gene family size was obtained under a linear duplication-transfer-loss model with selection. With the exception of genes involved in information processing, particularly translation, which are maintained by strong selection, the average selection coefficient for most non-parasitic genes is low albeit positive, compatible with the observed positive correlation between genome size and effective population size. Free-living microbes evolve under stronger selection for gene retention than parasites. Different classes of MGE show a broad range of fitness effects, from the nearly neutral transposons to prophages, which are actively eliminated by selection. Genes involved in anti-parasite defense, on average, incur a fitness cost to the host that is at least as high as the cost of plasmids. This cost is probably due to the adverse effects of autoimmunity and curtailment of horizontal gene transfer caused by the defense systems and selfish behavior of some of these systems, such as toxin-antitoxin and restriction-modification modules. Transposons follow a biphasic dynamics, with bursts of gene proliferation followed by decay in the copy number that is quantitatively captured by the model. The horizontal gene transfer to loss ratio, but not the duplication to loss ratio, correlates with genome size, potentially explaining the increased abundance of neutral and costly elements in larger genomes.SIGNIFICANCEEvolution of microbes is dominated by horizontal gene transfer and the incessant host-parasite arms race that promotes the evolution of diverse anti-parasite defense systems. The evolutionary factors governing these processes are complex and difficult to disentangle but the rapidly growing genome databases provide ample material for testing evolutionary models. Rigorous mathematical modeling of evolutionary processes, combined with computer simulation and comparative genomics, allowed us to elucidate the evolutionary regimes of different classes of microbial genes. Only genes involved in key informational and metabolic pathways are subject to strong selection whereas most of the others are effectively neutral or even burdensome. Mobile genetic elements and defense systems are costly, supporting the understanding that their evolution is governed by the same factors.

scholarly journals Discovery of multiple anti-CRISPRs uncovers anti-defense gene clustering in mobile genetic elements

2020 ◽  
Author(s):  
Rafael Pinilla-Redondo ◽  
Saadlee Shehreen ◽  
Nicole D. Marino ◽  
Robert D. Fagerlund ◽  
Chris M. Brown ◽  
...  
Keyword(s):  
Mobile Genetic Elements ◽  
Gene Clustering ◽  
Type I ◽  
Defense Gene ◽  
Genetic Elements ◽  
Defense Systems ◽  
Prokaryotic Genomes ◽  
New Type ◽  
Genomic Regions ◽  
Potential Exploitation

AbstractMany prokaryotes employ CRISPR-Cas systems to combat invading mobile genetic elements (MGEs). In response, some MGEs have evolved Anti-CRISPR (Acr) proteins to bypass this immunity, yet the diversity, distribution and spectrum of activity of this immune evasion strategy remain largely unknown. Here, we uncover 11 new type I anti-CRISPR genes encoded on numerous chromosomal and extrachromosomal mobile genetic elements within Enterobacteriaceae and Pseudomonas. Candidate genes were identified adjacent to anti-CRISPR associated gene 5 (aca5) and assayed against a panel of six type I systems: I-F (Pseudomonas, Pectobacterium, and Serratia), I-E (Pseudomonas and Serratia), and I-C (Pseudomonas), revealing the type I-F and/or I-E acr genes and a new aca (aca9). We find that acr genes not only associate with other acr genes, but also with inhibitors of distinct bacterial defense systems. These genomic regions appear to be “anti-defense islands”, reminiscent of the clustered arrangement of “defense islands” in prokaryotic genomes. Our findings expand on the diversity of CRISPR-Cas inhibitors and reveal the potential exploitation of acr loci neighborhoods for identifying new anti-defense systems.

scholarly journals The ESKAPE mobilome contributes to the spread of antimicrobial resistance and CRISPR-mediated conflict between mobile genetic elements

2022 ◽  
Author(s):  
João Botelho ◽  
Adrian Cazares ◽  
Hinrich Schulenburg
Keyword(s):  
Antibiotic Resistance Genes ◽  
Distribution Patterns ◽  
Mobile Genetic Elements ◽  
Human Pathogens ◽  
Systematic Analysis ◽  
Genetic Elements ◽  
General Importance ◽  
Species Specific ◽  
Eskape Pathogens ◽  
Asymmetrically Distributed

Mobile genetic elements (MGEs) mediate the shuffling of genes among organisms. They contribute to the spread of virulence and antibiotic resistance genes in human pathogens, including the particularly problematic group of ESKAPE pathogens, such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. Here, we performed the first systematic analysis of MGEs, including plasmids, prophages, and integrative and conjugative/mobilizable elements (ICEs/IMEs), in the ESKAPE pathogens. We characterized over 1700 complete ESKAPE genomes and found that different MGE types are asymmetrically distributed across these pathogens. While some MGEs are capable of exchanging DNA beyond the genus (and phylum) barrier, horizontal gene transfer (HGT) is mainly restricted by phylum or genus. We further observed that most genes on MGEs have unknown functions and show intricate distribution patterns. Moreover, AMR genes and anti-CRISPRs are overrepresented in the ESKAPE mobilome. Our results also underscored species-specific trends shaping the number of MGEs, AMR, and virulence genes across pairs of conspecific ESKAPE genomes with and without CRISPR-Cas systems. Finally, we found that CRISPR targets vary according to MGE type: while plasmid CRISPRs almost exclusively target other plasmids, ICEs/IME CRISPRs preferentially target ICEs/IMEs and prophages. Overall, our study highlights the general importance of the ESKAPE mobilome in contributing to the spread of AMR and mediating conflict among MGEs.

scholarly journals An ecological perspective on microbial genes of unknown function in soil

2021 ◽  
Author(s):  
Hannah Holland-Moritz ◽  
Chiara Vanni ◽  
Antonio Fernandez-Guerra ◽  
Andrew Bissett ◽  
Noah Fierer
Keyword(s):  
Unknown Function ◽  
Gene Clusters ◽  
Mobile Genetic Elements ◽  
Ecological Perspective ◽  
Substantial Portion ◽  
Functional Roles ◽  
Genetic Elements ◽  
Soil Microbial ◽  
Soil Communities ◽  
Ecological Associations

AbstractGenes that remain hypothetical, uncharacterized, and unannotated comprise a substantial portion of metagenomic datasets and are likely to be particularly prevalent in soils where poorly characterized taxa predominate. Documenting the prevalence, distribution, and potential roles of these genes of unknown function is an important first step to understanding their functional contributions in soil communities. We identified genes of unknown function from 50 soil metagenomes and analyzed their environmental distributions and ecological associations. We found that genes of unknown function are prevalent in soils, particularly fine-textured, higher pH soils that harbor greater abundances of Crenarchaeota, Gemmatimonadota, Nitrospirota, and Methylomirabilota. We identified 43 dominant (abundant and ubiquitous) gene clusters of unknown function and determined their associations with soil microbial phyla and other “known” genes. We found that these dominant unknown genes were commonly associated with microbial phyla that are relatively uncharacterized, with the majority of these dominant unknown genes associated with mobile genetic elements. This work demonstrates a strategy for investigating genes of unknown function in soils, emphasizes the biological insights that can be learned by adopting this strategy, and highlights specific hypotheses that warrant further investigation regarding the functional roles of abundant and ubiquitous genes of unknown function in soil metagenomes.

scholarly journals Genomic Stability and Genetic Defense Systems in Dolosigranulum pigrum , a Candidate Beneficial Bacterium from the Human Microbiome

mSystems ◽  
2021 ◽  
Author(s):  
Stephany Flores Ramos ◽  
Silvio D. Brugger ◽  
Isabel Fernandez Escapa ◽  
Chelsey A. Skeete ◽  
Sean L. Cotton ◽  
...  
Keyword(s):  
Human Life ◽  
Human Microbiome ◽  
Genomic Stability ◽  
Therapeutic Use ◽  
Content Type ◽  
Defense Systems ◽  
Beneficial Bacterium ◽  
Nasal Microbiota

Dolosigranulum pigrum is a candidate beneficial bacterium with potential for future therapeutic use. This is based on its positive associations with characteristics of health in multiple studies of human nasal microbiota across the span of human life.

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