On Inferring Additive and Replacing Horizontal Gene Transfers Through Phylogenetic Reconciliation

2020 ◽  
Author(s):  
Misagh Kordi ◽  
Soumya Kundu ◽  
Mukul S. Bansal
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Classification Accuracy ◽  
Software Package ◽  
Microbial Evolution ◽  
Homologous Gene ◽  
Gene Duplications ◽  
New Gene ◽  
Phylogenetic Reconciliation ◽  
The Impact

AbstractHorizontal gene transfer is one of the most important mechanisms for microbial evolution and adaptation. It is well known that horizontal gene transfer can be either additive or replacing depending on whether the transferred gene adds itself as a new gene in the recipient genome or replaces an existing homologous gene. Yet, all existing phylogenetic techniques for the inference of horizontal gene transfer assume either that all transfers are additive or that all transfers are replacing. This limitation not only affects the applicability and accuracy of these methods but also makes it difficult to distinguish between additive and replacing transfers.Here, we address this important problem by formalizing a phylogenetic reconciliation framework that simultaneously models both additive and replacing transfer events. Specifically, we (1) introduce the DTRL reconciliation framework that explicitly models both additive and replacing transfer events, along with gene duplications and losses, (2) prove that the underlying computational problem is NP-hard, (3) perform the first experimental study to assess the impact of replacing transfer events on the accuracy of the traditional DTL reconciliation model (which assumes that all transfers are additive) and demonstrate that traditional DTL reconciliation remains highly robust to the presence of replacing transfers, (4) propose a simple heuristic algorithm for DTRL reconciliation based on classifying transfer events inferred through DTL reconciliation as being replacing or additive, and (5) evaluate the classification accuracy of the heuristic under a range of evolutionary conditions. Thus, this work lays the methodological and algorithmic foundations for estimating DTRL reconciliations and distinguishing between additive and replacing transfers.An implementation of our heuristic for DTRL reconciliation is freely available open-source as part of the RANGER-DTL software package from https://compbio.engr.uconn.edu/software/ranger-dtl/.

Horizontal Gene Transfer in Microbial Evolution

2018 ◽  
pp. 527-533
Author(s):  
Johann Peter Gogarten ◽  
R. Thane Papke
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Microbial Evolution

Gene duplications and horizontal gene transfer during early evolution

1996 ◽  
Vol 26 (3-5) ◽  
pp. 284-285 ◽  
Author(s):  
J. Peter Gogarten ◽  
Elena Hilario ◽  
Lorraine Olendzenski
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Early Evolution ◽  
Gene Duplications

scholarly journals Adaptation by Ancient Horizontal Acquisition of Butyrate Metabolism Genes in Aggregatibacter actinomycetemcomitans

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Ahmed M. Moustafa ◽  
Senthil Kumar Velusamy ◽  
Lidiya Denu ◽  
Apurva Narechania ◽  
Daniel H. Fine ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Strong Association ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Short Chain ◽  
Oral Microbiota ◽  
Content Type ◽  
History Of ◽  
The Impact

ABSTRACT Like the bacterial residents of the human gut, it is likely that many of the species in the human oral microbiota have evolved to better occupy and persist in their niche. Aggregatibacter actinomycetemcomitans (Aa) is both a common colonizer of the oral cavity and has been implicated in the pathogenesis of periodontal disease. Here, we present a whole-genome phylogenetic analysis of Aa isolates from humans and nonhuman primates that revealed an ancient origin for this species and a long history of association with the Catarrhini, the lineage that includes Old World monkeys (OWM) and humans. Further genomic analysis showed a strong association with the presence of a short-chain fatty acid (SCFA) catabolism locus (atoRDAEB) in many human isolates that was absent in almost all nonhuman OWM isolates. We show that this locus was likely acquired through horizontal gene transfer. When grown under conditions that are similar to those at the subgingival site of periodontitis (anaerobic, SCFA replete), Aa strains with atoRDAEB formed robust biofilms and showed upregulation of genes involved in virulence, colonization, and immune evasion. Both an isogenic deletion mutant and nonhuman primate isolates lacking the ato locus failed to grow in a robust biofilm under these conditions, but grew well under the carbohydrate-rich conditions similar to those found above the gumline. We propose that the acquisition of the ato locus was a key evolutionary step allowing Aa to utilize SCFAs, adapt, and modulate subgingival disease. IMPORTANCE There has been considerable interest in the impact of short-chain fatty acids (SCFAs) on inflammatory effects related to the microbiome. Here, we present evidence that SCFAs may also be important in disease by providing an energy source or disease-associated cue for colonizing pathogens. We propose that SCFAs allow Aggregatibacter actinomycetemcomitans (Aa) to adapt to the subgingival anaerobic environment, which is the site of human periodontitis. Under anaerobic, SCFA-rich conditions, human-derived Aa strains that possess butyrate metabolism genes form strong biofilms and upregulate virulence genes. Our phylogenetic analysis highlights a long history of evolution of Aa with its primate hosts and suggests that the acquisition of butyrate metabolism genes may have been a critical step in allowing Aa to colonize a new niche and cause disease in humans. Overall, this study highlights the important role that horizontal gene transfer may play in microbial adaptation and the evolution of infectious disease.

A method to delineate de novo missense variants across pathways prioritizes genes linked to autism

2021 ◽  
Vol 13 (594) ◽  
pp. eabc1739
Author(s):  
Amanda Koire ◽  
Panagiotis Katsonis ◽  
Young Won Kim ◽  
Christie Buchovecky ◽  
Stephen J. Wilson ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Protein Function ◽  
De Novo ◽  
Autism Spectrum ◽  
Homologous Gene ◽  
Fitness Effect ◽  
Missense Variants ◽  
Whole Exome ◽  
New Gene ◽  
The Impact

Genotype-phenotype relationships shape health and population fitness but remain difficult to predict and interpret. Here, we apply an evolutionary action method to de novo missense variants in whole-exome sequences of individuals with autism spectrum disorder (ASD) to unravel genes and pathways connected to ASD. Evolutionary action predicts the impact of missense variants on protein function by measuring the fitness effect based on phylogenetic distances and substitution odds in homologous gene sequences. By examining de novo missense variants in 2384 individuals with ASD (probands) compared to matched siblings without ASD, we found missense variants in 398 genes representing 23 pathways that were biased toward higher evolutionary action scores than expected by random chance; these pathways were involved in axonogenesis, synaptic transmission, and neurodevelopment. The predicted fitness impact of de novo and inherited missense variants in candidate genes correlated with the IQ of individuals with ASD, even for new gene candidates. Taking an evolutionary action method, we detected those missense variants most likely to contribute to ASD pathogenesis and elucidated their phenotypic impact. This approach could be applied to integrate missense variants across a patient cohort to identify genes contributing to a shared phenotype in other complex diseases.

scholarly journals Novel “Superspreader” Bacteriophages Promote Horizontal Gene Transfer by Transformation

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Eric C. Keen ◽  
Valery V. Bliskovsky ◽  
Francisco Malagon ◽  
James D. Baker ◽  
Jeffrey S. Prince ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Microbial Evolution ◽  
Phage Infection ◽  
Resistant Bacteria ◽  
Natural Environments ◽  
Plasmid Transformation ◽  
Isolation And Characterization

ABSTRACT Bacteriophages infect an estimated 10 23 to 10 25 bacterial cells each second, many of which carry physiologically relevant plasmids (e.g., those encoding antibiotic resistance). However, even though phage-plasmid interactions occur on a massive scale and have potentially significant evolutionary, ecological, and biomedical implications, plasmid fate upon phage infection and lysis has not been investigated to date. Here we show that a subset of the natural lytic phage population, which we dub “superspreaders,” releases substantial amounts of intact, transformable plasmid DNA upon lysis, thereby promoting horizontal gene transfer by transformation. Two novel Escherichia coli phage superspreaders, SUSP1 and SUSP2, liberated four evolutionarily distinct plasmids with equal efficiency, including two close relatives of prominent antibiotic resistance vectors in natural environments. SUSP2 also mediated the extensive lateral transfer of antibiotic resistance in unbiased communities of soil bacteria from Maryland and Wyoming. Furthermore, the addition of SUSP2 to cocultures of kanamycin-resistant E. coli and kanamycin-sensitive Bacillus sp. bacteria resulted in roughly 1,000-fold more kanamycin-resistant Bacillus sp. bacteria than arose in phage-free controls. Unlike many other lytic phages, neither SUSP1 nor SUSP2 encodes homologs to known hydrolytic endonucleases, suggesting a simple potential mechanism underlying the superspreading phenotype. Consistent with this model, the deletion of endonuclease IV and the nucleoid-disrupting protein ndd from coliphage T4, a phage known to extensively degrade chromosomal DNA, significantly increased its ability to promote plasmid transformation. Taken together, our results suggest that phage superspreaders may play key roles in microbial evolution and ecology but should be avoided in phage therapy and other medical applications. IMPORTANCE Bacteriophages (phages), viruses that infect bacteria, are the planet’s most numerous biological entities and kill vast numbers of bacteria in natural environments. Many of these bacteria carry plasmids, extrachromosomal DNA elements that frequently encode antibiotic resistance. However, it is largely unknown whether plasmids are destroyed during phage infection or released intact upon phage lysis, whereupon their encoded resistance could be acquired and manifested by other bacteria (transformation). Because phages are being developed to combat antibiotic-resistant bacteria and because transformation is a principal form of horizontal gene transfer, this question has important implications for biomedicine and microbial evolution alike. Here we report the isolation and characterization of two novel Escherichia coli phages, dubbed “superspreaders,” that promote extensive plasmid transformation and efficiently disperse antibiotic resistance genes. Our work suggests that phage superspreaders are not suitable for use in medicine but may help drive bacterial evolution in natural environments.

scholarly journals Transductomics: sequencing-based detection and analysis of transduced DNA in pure cultures and microbial communities

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Manuel Kleiner ◽  
Brian Bushnell ◽  
Kenneth E. Sanderson ◽  
Lora V. Hooper ◽  
Breck A. Duerkop
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Microbial Communities ◽  
Microbial Evolution ◽  
Model Systems ◽  
Intestinal Microbiome ◽  
Mobile Dna ◽  
Pure Cultures ◽  
Taxonomic Range ◽  
Taxonomic Groups

Abstract Background Horizontal gene transfer (HGT) plays a central role in microbial evolution. Our understanding of the mechanisms, frequency, and taxonomic range of HGT in polymicrobial environments is limited, as we currently rely on historical HGT events inferred from genome sequencing and studies involving cultured microorganisms. We lack approaches to observe ongoing HGT in microbial communities. Results To address this knowledge gap, we developed a DNA sequencing-based “transductomics” approach that detects and characterizes microbial DNA transferred via transduction. We validated our approach using model systems representing a range of transduction modes and show that we can detect numerous classes of transducing DNA. Additionally, we show that we can use this methodology to obtain insights into DNA transduction among all major taxonomic groups of the intestinal microbiome. Conclusions The transductomics approach that we present here allows for the detection and characterization of genes that are potentially transferred between microbes in complex microbial communities at the time of measurement and thus provides insights into real-time ongoing horizontal gene transfer. This work extends the genomic toolkit for the broader study of mobile DNA within microbial communities and could be used to understand how phenotypes spread within microbiomes.

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