scholarly journals How environment shapes horizontal gene transfer

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Rama Bhatia ◽  
Hande Kirit ◽  
Jonathan Bollback
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Gene Dosage ◽  
Recipient Cell ◽  
Endogenous Gene ◽  
Fitness Effects ◽  
Serovar Typhimurium ◽  
A Cell ◽  
Evolutionary Fate

The evolutionary fate of a horizontal gene transfer (HGT) event is determined by its fitness on the recipient cell, i.e., whether it is beneficial, neutral or deleterious. The distribution of fitness effects (DFE), thus is a fundamental predictor of the outcome of an HGT event. The environment plays a considerable role in determining the fitness cost of a horizontally transferred gene. We have studied the fitness effects of genes transferred from Salmonella enterica serovar Typhimurium to Escherichia coli in six environments, that potentially represent the conditions experienced by the two species. The data suggests high variability of genes in different environments. Genes, whose fitness varies substantially between environments, may be able to persist in populations while being deleterious in one environment, they may be neutral or even beneficial in another environment, suggesting that environmental fluctuations may increase the likelihood of HGT. In addition to the in vitro environments, we are also looking at, how changes in the intrinsic environment of a cell, after an HGT event, could affect fitness. An increase in protein dosage due to functional similarity of the horizontally transferred gene to the endogenous gene can cause an imbalance in the cell, thereby leading to a negative fitness effect. By comparing the growth rates of each ortholog gene with the wild type strain, we can elucidate when gene dosage acts as a barrier to HGT.

scholarly journals Experimental Determination of Evolutionary Barriers to Horizontal Gene Transfer

2019 ◽  
Author(s):  
Hande Acar Kirit ◽  
Mato Lagator ◽  
Jonathan P. Bollback
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Protein Interactions ◽  
Evolutionary Dynamics ◽  
Horizontal Transmission ◽  
Protein Protein Interactions ◽  
Fitness Effects ◽  
Intrinsic Protein Disorder ◽  
Serovar Typhimurium

AbstractHorizontal gene transfer, the acquisition of genes across species boundaries, is a major source of novel phenotypes. Several barriers have been suggested to impede the likelihood of horizontal transmission; however experimental evidence is scarce. We measured the fitness effects of genes transferred from Salmonella enterica serovar Typhimurium to Escherichia coli, and found that most result in strong fitness costs. Previously identified evolutionary barriers — gene function and the number of protein-protein interactions — did not predict the fitness effects of transferred genes. In contrast, dosage sensitivity, gene length, and the intrinsic protein disorder significantly impact the likelihood of a successful horizontal transfer. While computational approaches have been successful in describing long-term barriers to horizontal gene transfer, our experimental results identified previously underappreciated barriers that determine the fitness effects of newly transferred genes, and hence their short-term eco-evolutionary dynamics.

scholarly journals Experimental determination of evolutionary barriers to horizontal gene transfer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hande Acar Kirit ◽  
Mato Lagator ◽  
Jonathan P. Bollback
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Protein Interactions ◽  
Evolutionary Dynamics ◽  
Horizontal Transmission ◽  
Protein Protein Interactions ◽  
New Host ◽  
Transfer Event ◽  
Fitness Effects ◽  
Serovar Typhimurium

Abstract Background Horizontal gene transfer, the acquisition of genes across species boundaries, is a major source of novel phenotypes that enables microbes to rapidly adapt to new environments. How the transferred gene alters the growth – fitness – of the new host affects the success of the horizontal gene transfer event and how rapidly the gene spreads in the population. Several selective barriers – factors that impact the fitness effect of the transferred gene – have been suggested to impede the likelihood of horizontal transmission, however experimental evidence is scarce. The objective of this study was to determine the fitness effects of orthologous genes transferred from Salmonella enterica serovar Typhimurium to Escherichia coli to identify the selective barriers using highly precise experimental measurements. Results We found that most gene transfers result in strong fitness costs. Previously identified evolutionary barriers — gene function and the number of protein-protein interactions — did not predict the fitness effects of transferred genes. In contrast, dosage sensitivity, gene length, and the intrinsic protein disorder significantly impact the likelihood of a successful horizontal transfer. Conclusion While computational approaches have been successful in describing long-term barriers to horizontal gene transfer, our experimental results identified previously underappreciated barriers that determine the fitness effects of newly transferred genes, and hence their short-term eco-evolutionary dynamics.

scholarly journals Trasposon Mediated Horizontal Gene Transfer (T-HGT) of Circulating Tumor DNA Reshapes MM Clonal Architecture

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3065-3065
Author(s):  
Munevver Cinar ◽  
Steven Flygare ◽  
Marina Mosunjac ◽  
Ganji Nagaraju ◽  
Dongkyoo Park ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Drug Sensitivity ◽  
Genetic Material ◽  
Host Cells ◽  
Response To Treatment ◽  
Hierarchical Architecture ◽  
Tumor Evolution ◽  
Sequencing Analysis

Spatial genetic heterogeneity is a characteristic phenomenon that influences multiple myeloma's (MM) phenotype and drug sensitivity (Rasche L. et al and Bolli N et al.). Hence, the branch model of tumor evolution is not sufficient to explain the disorganized architecture observed in MM. In this study, we investigated whether MM ctDNA horizontal gene transfer (HGT) affect tumor genetic architecture and drug sensitivity, resembling what is seen in prokaryotes, and elucidated the mechanisms involved in the mobilization of genetic material from one cell to another. We identified that plasma from patients with MM transmits drug sensitivity or resistance to cells in culture. This transmission of drug sensitivity is mediated by ctDNA transfer of oncogenes to a host cell. Importantly, in vitro and in vivo demonstrated that ctDNA mainly targets cells resembling the cell of origin (tropism). Karyotype spreads and whole genome sequencing demonstrated that once patients ctDNA encounters host cells, it migrates into the nucleus where it ultimately integrates into the cell's genome. Integration to the genome was confirmed to be targeted to myeloma cells. Further sequencing analysis of multiple MM samples identified ctDNA tropism and integration is dependent on the 5' and 3' end presence of transposable elements (TE), particularly of the MIR and ALUsq family. These results were further validated by TE mediated delivery of GFP into MM cells in vitro and HSVTK in tumors of mouse xenografts. In conclusion, this data indicates for the first time that TE mediates MM ctDNA HGT into homologous tumor cells shaping the hierarchical architecture of tumor clones and affecting tumor response to treatment. Therapeutically, this unique quality of ctDNA can be exploited for targeted gene therapeutic approaches in MM and potentially other cancers. Disclosures Bernal-Mizrachi: Kodikas Therapeutic Solutions, Inc: Equity Ownership; TAKEDA: Research Funding; Winship Cancer Institute: Employment, Patents & Royalties.

scholarly journals Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor inSalmonella entericaserovar Typhimurium

2018 ◽  
Vol 14 ◽  
pp. 2651-2664 ◽  
Author(s):  
Matthew J Styles ◽  
Helen E Blackwell
Keyword(s):  
Quorum Sensing ◽  
Small Molecules ◽  
Homoserine Lactone ◽  
Interspecies Interactions ◽  
Host Colonization ◽  
Serovar Typhimurium ◽  
Coordinate Group ◽  
A Cell ◽  
Production Host

Quorum sensing (QS) allows many common bacterial pathogens to coordinate group behaviors such as virulence factor production, host colonization, and biofilm formation at high population densities. This cell–cell signaling process is regulated byN-acyl L-homoserine lactone (AHL) signals, or autoinducers, and LuxR-type receptors in Gram-negative bacteria. SdiA is an orphan LuxR-type receptor found inEscherichia, Salmonella, Klebsiella, and Enterobactergenera that responds to AHL signals produced by other species and regulates genes involved in several aspects of host colonization. The inhibition of QS using non-native small molecules that target LuxR-type receptors offers a non-biocidal approach for studying, and potentially controlling, virulence in these bacteria. To date, few studies have characterized the features of AHLs and other small molecules capable of SdiA agonism, and no SdiA antagonists have been reported. Herein, we report the screening of a set of AHL analogs to both uncover agonists and antagonists of SdiA and to start to delineate structure–activity relationships (SARs) for SdiA:AHL interactions. Using a cell-based reporter of SdiA inSalmonella entericaserovar Typhimurium, several non-natural SdiA agonists and the first set of SdiA antagonists were identified and characterized. These compounds represent new chemical probes for exploring the mechanisms by which SdiA functions during infection and its role in interspecies interactions. Moreover, as SdiA is highly stable when produced in vitro, these compounds could advance fundamental studies of LuxR-type receptor:ligand interactions that engender both agonism and antagonism.

scholarly journals Minimal and RNA-free RNase P in Aquifex aeolicus

2017 ◽  
Vol 114 (42) ◽  
pp. 11121-11126 ◽  
Author(s):  
Astrid I. Nickel ◽  
Nadine B. Wäber ◽  
Markus Gößringer ◽  
Marcus Lechner ◽  
Uwe Linne ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Rnase P ◽  
Aquifex Aeolicus ◽  
Trna Processing ◽  
Hyperthermophilic Bacterium ◽  
Domains Of Life

RNase P is an essential tRNA-processing enzyme in all domains of life. We identified an unknown type of protein-only RNase P in the hyperthermophilic bacterium Aquifex aeolicus: Without an RNA subunit and the smallest of its kind, the 23-kDa polypeptide comprises a metallonuclease domain only. The protein has RNase P activity in vitro and rescued the growth of Escherichia coli and Saccharomyces cerevisiae strains with inactivations of their more complex and larger endogenous ribonucleoprotein RNase P. Homologs of Aquifex RNase P (HARP) were identified in many Archaea and some Bacteria, of which all Archaea and most Bacteria also encode an RNA-based RNase P; activity of both RNase P forms from the same bacterium or archaeon could be verified in two selected cases. Bioinformatic analyses suggest that A. aeolicus and related Aquificaceae likely acquired HARP by horizontal gene transfer from an archaeon.

scholarly journals Horizontal Gene Transfer of Functional Type VI Killing Genes by Natural Transformation

2017 ◽  
Author(s):  
Jacob Thomas ◽  
Samit S. Watve ◽  
William C. Ratcliff ◽  
Brian K. Hammer
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Horizontal Transfer ◽  
Direct Injection ◽  
Spatially Explicit ◽  
Type Vi Secretion System ◽  
Effector Genes ◽  
Type Vi Secretion ◽  
A Cell ◽  
Explicit Simulation

AbstractHorizontal gene transfer can have profound effects on bacterial evolution by allowing individuals to rapidly acquire adaptive traits that shape their strategies for competition. One strategy for intermicrobial antagonism often used by Proteobacteria is the genetically-encoded contact-dependent Type VI secretion system (T6SS); a weapon used to kill heteroclonal neighbors by direct injection of toxic effectors. Here, we experimentally demonstrate thatVibrio choleraecan acquire new T6SS effector genes via horizontal transfer and utilize them to kill neighboring cells. Replacement of one or more parental alleles with novel effectors allows the recombinant strain to dramatically outcompete its parent. Through spatially-explicit simulation modeling, we show that the HGT is risky: transformation brings a cell into conflict with its former clonemates, but can be adaptive when superior T6SS alleles are acquired. More generally, we find that these costs and benefits are not symmetric, and that high rates of HGT can act as hedge against competitors with unpredictable T6SS efficacy. We conclude that antagonism and horizontal transfer drive successive rounds of weapons-optimization and selective sweeps, dynamically shaping the composition of microbial communities.

scholarly journals Complex Evolution of Light-Dependent Protochlorophyllide Oxidoreductases in Aerobic Anoxygenic Phototrophs: Origin, Phylogeny, and Function

2020 ◽  
Author(s):  
Olga Chernomor ◽  
Lena Peters ◽  
Judith Schneidewind ◽  
Anita Loeschcke ◽  
Esther Knieps-Grünhagen ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Phylogenetic Analyses ◽  
Oxygenic Photosynthesis ◽  
Protochlorophyllide Oxidoreductase ◽  
Transfer Event ◽  
Anoxygenic Phototrophs ◽  
And Function

Abstract Light-dependent protochlorophyllide oxidoreductase (LPOR) and dark-operative protochlorophyllide oxidoreductase are evolutionary and structurally distinct enzymes that are essential for the synthesis of (bacterio)chlorophyll, the primary pigment needed for both anoxygenic and oxygenic photosynthesis. In contrast to the long-held hypothesis that LPORs are only present in oxygenic phototrophs, we recently identified a functional LPOR in the aerobic anoxygenic phototrophic bacterium (AAPB) Dinoroseobacter shibae and attributed its presence to a single horizontal gene transfer event from cyanobacteria. Here, we provide evidence for the more widespread presence of genuine LPOR enzymes in AAPBs. An exhaustive bioinformatics search identified 36 putative LPORs outside of oxygenic phototrophic bacteria (cyanobacteria) with the majority being AAPBs. Using in vitro and in vivo assays, we show that the large majority of the tested AAPB enzymes are genuine LPORs. Solution structural analyses, performed for two of the AAPB LPORs, revealed a globally conserved structure when compared with a well-characterized cyanobacterial LPOR. Phylogenetic analyses suggest that LPORs were transferred not only from cyanobacteria but also subsequently between proteobacteria and from proteobacteria to Gemmatimonadetes. Our study thus provides another interesting example for the complex evolutionary processes that govern the evolution of bacteria, involving multiple horizontal gene transfer events that likely occurred at different time points and involved different donors.

scholarly journals Horizontal Gene Transfer of ftsI, Encoding Penicillin-Binding Protein 3, in Haemophilus influenzae

2007 ◽  
Vol 51 (5) ◽  
pp. 1589-1595 ◽  
Author(s):  
Sho Takahata ◽  
Takashi Ida ◽  
Nami Senju ◽  
Yumiko Sanbongi ◽  
Aiko Miyata ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Haemophilus Influenzae ◽  
Binding Protein ◽  
Resistant Mutant ◽  
Penicillin Binding Protein ◽  
Genetic Transfer ◽  
Complete Sequences

ABSTRACT Horizontal gene transfer has been identified in only a small number of genes in Haemophilus influenzae, an organism which is naturally competent for transformation. This report provides evidence for the genetic transfer of the ftsI gene, which encodes penicillin-binding protein 3, in H. influenzae. Mosaic structures of the ftsI gene were found in several clinical isolates of H. influenzae. To identify the origin of the mosaic sequence, complete sequences of the corresponding gene from seven type strains of Haemophilus species were determined. Comparison of these sequences with mosaic regions identified a homologous recombination of the ftsI gene between H. influenzae and Haemophilus haemolyticus. Subsequently, ampicillin-resistant H. influenzae strains harboring identical ftsI sequences were genotyped by pulsed-field gel electrophoresis (PFGE). Divergent PFGE patterns among β-lactamase-nonproducing ampicillin-resistant (BLNAR) strains from different hospitals indicated the potential for the genetic transfer of the mutated ftsI gene between these isolates. Moreover, transfer of the ftsI gene from BLNAR strains to β-lactamase-nonproducing ampicillin-susceptible (BLNAS) H. influenzae strains was evaluated in vitro. Coincubation of a BLNAS strain (a rifampin-resistant mutant of strain Rd) and BLNAR strains resulted in the emergence of rifampin- and cefdinir-resistant clones at frequencies of 5.1 × 10−7 to 1.5 × 10−6. Characterization of these doubly resistant mutants by DNA sequencing of the ftsI gene, susceptibility testing, and genotyping by PFGE revealed that the ftsI genes of BLNAR strains had transferred to BLNAS strains during coincubation. In conclusion, horizontal transfer of the ftsI gene in H. influenzae can occur in an intraspecies and an interspecies manner.

scholarly journals Whole-Genome Analysis ofSalmonella entericaSerovar Typhimurium T000240 Reveals the Acquisition of a Genomic Island Involved in Multidrug Resistance via IS1Derivatives on the Chromosome

2010 ◽  
Vol 55 (2) ◽  
pp. 623-630 ◽  
Author(s):  
Hidemasa Izumiya ◽  
Tsuyoshi Sekizuka ◽  
Hideo Nakaya ◽  
Masumi Taguchi ◽  
Akio Oguchi ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Genome Analysis ◽  
Genomic Island ◽  
Whole Genome ◽  
Class 1 Integron ◽  
Serovar Typhimurium ◽  
Class 1

ABSTRACTSalmonella entericaserovar Typhimurium is frequently associated with life-threatening systemic infections, and the recent global emergence of multidrug resistance inS. entericaisolates from agricultural and clinical settings has raised concerns. In this study, we determined the whole-genome sequence of fluoroquinolone-resistantS. entericaserovar Typhimurium T000240 strain (DT12) isolated from human gastroenteritis in 2000. Comparative genome analysis revealed that T000240 displays high sequence similarity to strain LT2, which was originally isolated in 1940, indicating that progeny of LT2 might be reemerging. T000240 possesses a unique 82-kb genomic island, designated as GI-DT12, which is composed of multidrug resistance determinants, including a Tn2670-like composite transposon (class 1 integron [intI1,blaoxa-30,aadA1,qacEΔ1, andsul1], mercury resistance proteins, and chloramphenicol acetyltransferase), a Tn10-like tetracycline resistance protein (tetA), the aerobactin iron-acquisition siderophore system (lutAandlucABC), and an iron transporter (sitABCD). Since GI-DT12 is flanked by IS1derivatives, IS1-mediated recombination likely played a role in the acquisition of this genomic island through horizontal gene transfer. The aminoglycoside-(3)-N-acetyltransferase (aac(3)) gene and a class 1 integron harboring thedfrA1gene cassette responsible for gentamicin and trimethoprim resistance, respectively, were identified on plasmid pSTMDT12_L and appeared to have been acquired through homologous recombination with IS26. This study represents the first characterization of the unique genomic island GI-DT12 that appears to be associated with possible IS1-mediated recombination inS. entericaserovar Typhimurium. It is expected that future whole-genome studies will aid in the characterization of the horizontal gene transfer events for the emergingS. entericaserovar Typhimurium strains.

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