What was the outcome of horizontal gene transfer




















Nakabachi, A. The kilobase genome of the bacterial endosymbiont Carsonella. Science , Tamames, J. The frontier between cell and organelle: genome analysis of Candidatus Carsonella ruddii. McCutcheon, J. Parallel genomic evolution and metabolic interdependence in an ancient symbiosis. USA , — Dujon, B. Genome evolution in yeasts.

Nature , 35—44 Article PubMed Google Scholar. Hall, C. Contribution of horizontal gene transfer to the evolution of Saccharomyces cerevisiae. Cell 4 , — Ricard, G. Horizontal gene transfer from bacteria to rumen ciliates indicates adaptation to their anaerobic, carbohydrates-rich environment. BMC Genomics 7 , 22 The rumen gut is an environment that is rich in bacteria—protist interactions, and this study shows that rumen ciliates are taking up bacterial genes at a high frequency. You are what you eat: a gene transfer ratchet could account for bacterial genes in eukaryotic nuclear genomes.

Archibald, J. Lateral gene transfer and the evolution of plastid-targeted proteins in the secondary plastid-containing alga Bigelowiella natans.

One of the first studies to describe widespread HGT to a nuclear genome, in this case showing that plastid-targeted genes are derived from many different kinds of algae and bacteria. Watkins, R. The frequency of eubacterium-to-eukaryote lateral gene transfers shows significant cross-taxa variation within amoebozoa.

Lateral gene transfer and metabolic adaptation in the human parasite Trichomonas vaginalis. Are there bugs in our genome? Kondrashov, F.

Evolution of glyoxylate cycle enzymes in metazoa: evidence of multiple horizontal transfer events and pseudogene formation. Direct 1 , 31 Nakashima, K. The evolutionary origin of animal cellulose synthase. Genes Evol. Berriman, M. The genome of the African trypanosome Trypanosoma brucei. Douzery, E. The timing of eukaryotic evolution: does a relaxed molecular clock reconcile proteins and fossils?

Gene transfers from nanoarchaeota to an ancestor of diplomonads and parabasalids. A genomic survey of the fish parasite Spironucleus salmonicida indicates genomic plasticity among diplomonads and significant lateral gene transfer in eukaryote genome evolution.

BMC Genomics 8 , 51 Dozens of putative HGTs were identified in the genome of one diplomonad, with most of these events pre-dating the divergence of the two major lineages of diplomonads and some apparently pre-dating the divergence of diplomonads and parabasalians.

Most transferred genes encode metabolic proteins and were acquired from bacteria, but a significant minority seem to be eukaryote-to-eukaryote transfers.

Derelle, E. Genome analysis of the smallest free-living eukaryote Ostreococcus tauri unveils many unique features. Phylogenetic analyses of diplomonad genes reveal frequent lateral gene transfers affecting eukaryotes.

Pyruvate-phosphate dikinase of oxymonads and parabasalia and the evolution of pyrophosphate-dependent glycolysis in anaerobic eukaryotes. Carlton, J. Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis. Morrison, H. Genomic minimalism in the early diverging intestinal parasite Giardia lamblia.

Loftus, B. The genome of the protist parasite Entamoeba histolytica. Genome sequencing of anaerobic eukaryotic parasites also see references 64 and 65 has confirmed the conclusion, which was based on earlier, single-gene studies, that HGT has had a major role in the ad hoc assembly of the unusual metabolic pathways of these organisms.

Eichinger, L. The genome of the social amoeba Dictyostelium discoideum. Nature , 43—57 Waller, R. Lateral gene transfer of a multigene region from cyanobacteria to dinoflagellates resulting in a novel plastid-targeted fusion protein. Evolutionary analyses of the small subunit of glutamate synthase: gene order conservation, gene fusions, and prokaryote-to-eukaryote lateral gene transfers. Cell 1 , — Rice, D.

An exceptional horizontal gene transfer in plastids: gene replacement by a distant bacterial paralog and evidence that haptophyte and cryptophyte plastids are sisters. BMC Biol. In contrast to plant mitochondria, this large-scale analysis of HGT in plastid genomes revealed very little transfer.

One case that was identified, however, is an important, rare character that serves to phylogenetically unite two major groups of algae. Khan, H. Plastid genome sequence of the cryptophyte alga Rhodomonas salina CCMP lateral transfer of putative DNA replication machinery and a test of chromist plastid phylogeny.

Bevan, R. Bachvaroff, T. Dinoflagellate expressed sequence tags data indicate massive trasfer of chloroplast genes to the nuclear genome. Protist , 65—78 Keeling, P. Lateral transfer at the gene and subgenic levels in the evolution of eukaryotic enolase. USA 98 , — A tertiary plastid uses genes from two endosymbionts. Some dinoflagellates have a complex history of replacing their plastids with new ones from other lineages.

Here it is shown that genes derived from both plastids can be retained in the nuclear genome and their products also targeted to the new plastid, making its proteome chimeric. Rogers, M. Lateral gene transfer and re-compartmentalisation of Calvin cycle enzymes in plants and algae.

Hackett, J. Migration of the plastid genome to the nucleus in a peridinin dinoflagellate. Phylogenetic history of plastid-targeted proteins in the peridinin-containing dinoflagellate Heterocapsa triquetra.

Evolution of filamentous plant pathogens: gene exchange across eukaryotic kingdoms. Fungal and oomycete plant pathogens are distantly related but have many mechanistic similarities, and here it is shown that several convergent characteristics of their pathogenicity and feeding might be due to transfer of genes between them.

Friesen, T. Emergence of a new disease as a result of interspecific virulence gene transfer. Nature Genet. Virulence-related factors have been observed to transfer in several systems, including fungi, but in this case a virulence factor has moved from one fungus to another so recently that it can be dated to around , when it led to the emergence of a new disease.

Inderbitzin, P. Lateral transfer of mating system in Stemphylium. Slot, J. Horizontal transfer of a nitrate assimilation gene cluster and ecological transitions in fungi: a phylogenetic study. Simpson, A. Lateral transfer of the gene for a widely used marker, alpha-tubulin, indicated by a milti-protein study of the phylogenetic position of Andalucia Excavata.

Paoletti, M. Selective acquisition of novel mating type and vegetative incompatibility genes via interspecies gene transfer in the globally invading eukaryote Ophiostoma novo-ulmi. The reacquisition of biotin prototrophy in Saccharomyces cerevisiae involved horizontal gene transfer, gene duplication and gene clustering. Genetics , — Kavanaugh, L. Recent evolution of the human pathogen Cryptococcus neoformans by intervarietal transfer of a gene fragment.

A class of eukaryotic GTPase with a punctate distribution suggesting multiple functional replacements of translation elongation factor 1alpha. A complex and punctate distribution of three eukaryotic genes derived by lateral gene transfer. There are many examples of relatively simple bacteria—eukaryote HGT events, but in this paper broader sampling of three cases shows that complex, multiple transfer events might often seem to be simpler than they really are, and that transfer between eukaryotes might be more common than we think.

Nosenko, T. Horizontal gene transfer in chromalveolates. Alvarez, N. Phylogeographic support for horizontal gene transfer involving sympatric bruchid species. Direct 1 , 21 Jenkins, C. Genes for the cytoskeletal protein tubulin in the bacterial genus Prosthecobacter. Tubulins are hallmark proteins of the eukaryotic cytoskeleton, so it was surprising to find that this bacterial genome had acquired both alpha- and beta-tubulin genes by HGT, and that the proteins seem to retain some structural function.

Schlieper, D. Sontag, C. Cell Biol. Guljamow, A. Horizontal gene transfer of two cytoskeletal elements from a eukaryote to a cyanobacterium. Similar to reference 91, the cytoskeletal protein actin was thought to be unique to eukaryotes, but this cyanobacterium was found to have taken up genes for actin and actin accessory proteins, which are now used in a structural capacity.

Horizontal transfer of a eukaryotic plastid-targeted protein gene to cyanobacteria. Many eukaryotic genes are derived from the plastid endosymbiont, but here a eukaryotic gene that took over plastid function has also been transferred back to cyanobacteria, where it integrated into the genome adjacent to its bacterial analogue.

Gamieldien, J. Eukaryotic genes in Mycobacterium tuberculosis could have a role in pathogenesis and immunomodulation. Kinsella, R. Eukaryotic genes in Mycobacterium tuberculosis? Possible alternative explanations. Huang, J. Ancient horizontal gene transfer can benefit phylogenetic reconstruction. Stechmann, A. The glycolytic pathway of Trimastix pyriformis is an evolutionary mosaic. Unique phylogenetic relationships of glucokinase and glucosephosphate isomerase of the amitochondriate eukaryotes Giardia intestinalis , Spironucleus barkhanus and Trichomonas vaginalis.

Gene , — Ledent, V. Comparative genomics of the class 4 histone deacetylase family indicates a complex evolutionary history. Multiple gene phylogenies support the monophyly of cryptomonad and haptophyte host lineages. Phylogenomic analysis supports the monophyly of cryptophytes and haptophytes and the association of rhizaria with chromalveolates.

The presence of a haloarchaeal type tyrosyl-tRNA synthetase marks the opisthokonts as monophyletic. Gene replacement of fructose-1,6-bisphosphate aldolase FBA supports a single photosynthetic ancestor of chromalveolates.

Cell 3 , — Berney, C. A molecular time-scale for eukaryote evolution recalibrated with the continuous microfossil record. Hao, W. Patterns of bacterial gene movement. The fate of laterally transferred genes: life in the fast lane to adaptation or death.

Jain, R. Horizontal gene transfer among genomes: the complexity hypothesis. USA 96 , — The diversity and evolutionary history of plastids and their hosts. Reyes-Prieto, A. The origin and establishment of the plastid in algae and plants. Did an ancient chlamydial endosymbiosis facilitate the establishment of primary plastids? Genome Biol. Stiller, J. Plastid endosymbiosis, genome evolution and the origin of green plants. Trends Plant Sci. Jumping genes and shrinking genomes — probing the evolution of eukaryotic photosynthesis with genomics.

Ishida, K. Second- and third-hand chloroplasts in dinoflagellates: phylogeny of oxygen-evolving enhancer 1 PsbO protein reveals replacement of a nuclear-encoded plastid gene by that of a haptophyte tertiary endosymbiont. Since the Tremblaya has been affected by the degeneration process over years of evolution, its correlation with Moranella compensates for the lost genes which are mostly involved in essential amino acid synthesis and metabolic functions Husnik et al.

The way organisms can survive in arsenic-rich environments is a clear example of cross-kingdom HGT that enables extremophilic eukaryote to adapt to life, as it has horizontally received ArsM As III SAM methyltransferase form bacteria or archaea. Thus, the transfer and diffusion of arsM genes horizontally from bacteria to other kingdoms have made it possible to resist the toxicity of this metal.

It has been observed that in addition to the arsM genes that exhibit preserved S-adenosylmethionine-binding motifs to transport methyl to As III , three preserved cysteine residues of ArsM protein have also been detected in positions Cys72, Cys, and Cys in the thermophilic algae Cyanidioschyzon merolae sp. Likewise, Helicobacter pylori , the pathogenic gastric bacterium, uses the transition of nickel metal to enter and survive in the stomach.

The common ancestor of H. Nickel is the cofactor for urease enzyme. Urease generates carbon dioxide CO 2 and ammonia NH3 buffers via urea hydrolysis which can neutralize the acidic conditions of the stomach, and subsequently adapt bacteria to the gastric acidic environment Fischer F.

Hypothenemus hampei , also known as a coffee berry borer, is a serious coffee pest that causes a lot of damage annually to the coffee industry around the world. The invasive beetle obtains this feature through the HhMAN1 gene gain from its gut bacteria. The presence of antibiotic-resistant bacteria ARB or ARGs in the environment and their subsequent acquisition by clinically important microorganisms, such as plants, is a serious health-related issue.

Soil fungi is shown to cause the transfer and distribution of bacteria in different parts of the soil. Naturally, fungi can spread over distances and can enrich bacteria by harboring cryptic- and nutrition-assisting plasmids in their mycosphere. Subsequently, the wave of ARGs spread is formed in humans with uncontrolled use of antibiotics, and also via the food chain. Agrobacterium tumefaciens is a clear example of HGT from bacteria to eukaryotes. This Gram-negative bacterium is able to transfer and merge DNA into plant genomes, causing crown-gall disease.

To this, the physical attachment of Agrobacterium to the cell wall of the plant is required to insert its T-DNA. This secretion system has the ability to spread the antibiotic resistance by the transfer of plasmids.

Later, this microorganism was exploited as a useful transfer system for genetic engineering. In this way, bacteria are capable of changing and evolving eukaryotes genomes mediated by HGT Fronzes et al.

As a subset of TEs, endogenous retroviruses ERVs have been integrated into the human genome by retroviral infections of the germline cells of our ancestors where, over a long period of evolutionary time, each REV is dispersed across the genome in hundreds to thousands of repetitive copies Wallau et al. Nonetheless, transcriptome analyses of somatic tissues surrounding tumor cells indicated co-expression of genes with TEs, extending the idea that transposon is expressed in both somatic and germ-line cells Chung et al.

Co-opted by the host during evolution and having the capability of self-duplication and mobilization, ERVs provide a massive pool of autonomous gene regulatory modules, indispensable for normal regulation of genes and gene networks. Examples include pmediated regulation Wang et al. Accordingly, besides their wide implication in normal gene regulation processes and their application as useful tools for genome editing and gene therapy purposes, on the dark side, the high rate of transposition rate Romanish et al.

They also adversely affect the prospect of stem cell-based therapies Schumann et al. In cancers, hypomethylation Ross et al. During onco-exaptation, silent TEs can be epigenetically reactivated to promote cancer. To date, analysis of the prevalence of TE onco-exaptation events across 7, tumors and normal datasets from 15 cancer types resulted in the identification of oncogenes out of TE cryptic promoter-activation events across 3, tumors.

A study on genomic instability pathways arising from retrotransposon insertions in colorectal cancer CRC revealed highly variable retrotransposon activity among tumors and identified recurrent insertions in 15 known cancer genes. Clinically, the high number of insertions are independently associated with poor disease-specific survival Cajuso et al. Human stem cells are indispensable for most basic, clinical, and translational research, such as gene therapy and regenerative medicine.

However, they are wider in the clinic and are still limited by their potential risks due to genomic instability and tumorigenesis concerns Schumann et al. Owing to their self non-self -mobilizing potential, ERs are used as genetic engineering toolkits to introduce foreign DNA transgene to desired genomic regions in target cells.

Moreover, L1 has a role in the normal development of the embryo. After fertilization, global chromatin accessibility at the beginning of development by L1 transcriptional activation is important for normal embryonic development Jachowicz et al.

Also, the L1 RNA is required for repression of the transcriptional program specific to the 2-cell embryo and promotes exit from the 2-cell stage Percharde et al. Genotoxicity concerns for retrotransposon-mediated gene transfer are contradictory and reviewed in detail elsewhere Schumann et al. Random L1 mobilization in our genome can result in numerous disorders. These disorders are caused by the mutagenic activity of non-LTR retrotransposons, with a rate of 1— pathogenic human mutations due to L1-mediated retrotransposition events.

A complete list of ER-related human diseases can be found in Hancks and Kazazian Although specific TE-derived products can result in different consequences, there is a common pathogenic reaction, known as general inflammatory response.

In this section, we review the implication of newly emerged HGT tools adopted by eukaryotic cells to promote the emergence of beneficial traits as well as evolving numerous human-related maladies, in particular cancer.

Plants, in particular parasitic plants, accept a large quantity of genes horizontally. In parasitic plants, such a genome exchange is partly due to the food dependency to their host. Parasitic plants penetrate the tissues of donor plants by their haustorium to intake nutrients along with their genetic material. Thus, HGT monitoring will help to control the generation and function of parasitic plants, which is one of the most important agricultural problems in the world. DNA transferred horizontally can lead to the adaptive evolution of the recipient plants.

Results from transcriptome analysis of three parasitic members of Orobanchaceae Triphysaria versicolor , Striga hermonthica , and Phelipanche aegyptiaca and a non-parasitic member Lindenbergia showed 52 DNA non-sexual transfers between the parasite members of Orobanchaceae and their hosts.

These data show that the greater dependence of parasitic plants on their hosts might increase the chance for HGT, and HGT occurs more significantly in heterotrophic plants than non-parasitic plants Yang et al. Entering a large number of genes into the Amborella trichopoda mitochondrial genome by angiosperm, mosses and green algae as donors Rice et al. The issue of the transmittance of mitochondrial cytochrome c oxidase I COX1 group I introns into the Araceae family has already been investigated by Cusimano et al.

They demonstrated that fungi donate the introns into these flowering plants to promote the evolution of angiosperms. Similarly, phylogenetic studies demonstrate the distribution of the hAT superfamily DNA transposons horizontally between Drosophila species Schaack et al.

A paper by Ivancevic et al. Their research team traced and scrutinized these two foreign genes in a large number of eukaryotes genomes and showed evidence that they have identified for the first time the horizontal transmission in L1 elements. Also, they stated that plenty of lateral BovB elements are transferred between various species Ivancevic et al.

This is important as these events are actively involved in cancer progression and metastasis outbreak. In this section, we discuss the implication of HGT mediators including EVs exosomes , apoptotic bodies, and cfDNA in the emergence and progression of cancer, as well as the development of drug resistance. Evidence suggests that apoptotic cells derived from dying cells tumor cells can laterally transfer complex information to other cells, as they are shown to carry various cargoes including DNA, RNA, and protein.

Further, changes in the outer membrane of apoptotic cells can induce neighboring cells to become phagocytic de la Taille et al.

The consequence of apoptotic-mediated information transfer is not always pathologic, as in the case of bone remodeling which occurs each 2-weeks, a large number of apoptotic bodies are produced by mature osteoclasts. Earlier experiments indicated that oncogenic DNA can be transferred to cells by phagocytosis of apoptotic bodies. Results showed that apoptotic bodies derived from EBV-carrying B lymphocytes when cocultured with other cells e. Thus, HGT mediated by apoptotic cells can be a route for infection of cells that lack the receptor for the virus Holmgren et al.

A similar experiment is reported where DNA coding for the ARGs hygr-r can be transferred by apoptotic prostate cells to the Neomycin-resistant and bcl-2 overexpressing LNCaP prostate cells resulting in dual-antibiotic resistant prostate cancer cell clones de la Taille et al.

Uptake of apoptotic bodies derived from H-rasV and human c-myc-transfected rat fibroblasts by pnegative murine phagocytic cells results in loss of contact inhibition in vitro , aneuploidy, and the accumulation of the genetic changes that spark tumor formation in vivo Bergsmedh et al.

Further studies indicated that besides DNase II, the activity of Chk2, p53, and p21 signaling pathways can counteract propagation of apoptotic bodies-derived oncogenic DNA, thus it forms a genetic block against transformation and malignant phenotype Bergsmedh et al. Besides apoptotic bodies, cfDNA is another precious tool with an implication in diagnosis, prognosis, and monitoring of cancer. Also, larger DNA up to 10, bp with a necrotic cell origin is detected in cancer patients Jahr et al.

Various experiments have documented the oncogenic potential of cfDNA on normal cells. Thus, recipient cell genetic alteration with the potential to derive tumorigenicity and development of tumors are among the most serious subjects related to HDT Trejo-Becerril et al. Viral DNA integration into the human genome is an accepted fact, however, new studies indicated integration of bacterial DNA into the human somatic genome. This observation has now prompted a new hypothesis that the origin of cancer cells are bacteria.

It equally questions the source of primary cancer cells PCCs and secondary metastatic cancer cells SCCs which are proposed to be originated from the senescent normal cells and cancer cells, respectively. This observation suggests bacteria as the mighty origin of cancer cells Dong and Xing, Additionally, there is clinical evidence that bacterial DNA integrates into the human somatic genome through an RNA intermediate, as insertion of Acinetobacter and Pseudomonas genetic materials into human genome by HGT is validated which is causative to the development of acute myeloid leukemia AML and stomach adenocarcinoma, respectively Riley et al.

Also, data analysis of public cancer genome sequence data confirmed an association between the presence of mycobacterium tuberculosis complex in the glioblastoma multiforme GBM and ovarian serous cystadenocarcinoma OV samples, as well as the presence of Ralstonia spp. One of the most critical factors in tumor formation and development is mitochondrial respiration affecting the effective extension of metastasis.

Notably, the results of the conducted studies in this field point to the fact that tumor cells receive horizontally the mtDNA from other cells of the body to improve the cellular respiration conditions Berridge et al.

Cargo can be integrated on the outer or inner layer of the vesicle phospholipid membrane through anchoring proteins or can be packed inside the vesicle. Besides normal cells, apoptotic cell-derived extracellular vesicles ApoEVs are also described as containing nuclear materials and mitochondria and presenting cell-specific markers on the surface, which enable tracking of the cell of origin Jiang et al. Interestingly, EVs are shown to mediate the horizontal transfer and integration of RNA intermediates into the human genome.

To this, human cancer cells were transfected with an expression construct containing a retrotransposition-competent human L1 tagged with a reporter gene. Further analysis of isolated EVs showed enrichment of L1-derived reporter RNA transcripts from cancer cells expressing active L1 retrotransposition Kawamura et al.

Discovering the tumor-derived exosomes in cancerous mice revealed the releasing of epidermal growth factor receptor EGFR in host macrophages which cause a decrease in interferon-1 gene expression, and thereby the immune response is reduced against viral infection Gao et al. Thus, tumor cells can transfer activated EGFR through EVs to the host macrophage to dampen innate immunity response, rendering the host immunocompromised.

Initial experiments validating genomic DNA transfer of a model gene by exosomes comes from the study in which a lentiviral vector encoding Arabidopsis thaliana-DNA A. Further quantification and verification of PCR-products from the recipient cell suggested stable integration of A. Complex exchange of genetic information is evidenced in the pathogenesis of cancer. Likewise, microRNA-containing EVs derived from the sera of patients with colorectal cancer as well as HT29 colon cancer cells can induce the transformation of fibroblasts into colon carcinoma cells Abdouh et al.

In this view, a therapeutic strategy can be envisioned by targeting cancer-derived EVs. Finally, depletion of EVs, as evidenced by their preferential internalization by macrophages, was capable of reducing metastatic burden in a human breast cancer xenograft mouse model Nishida-Aoki et al.

As EVs are present in all fluids of living animals, exosome-mediated HGT is the driving force behind mammalian genome evolution which can be translated into cancer development as well as adaptation and drug resistance Baghban et al.

Engineered exosomes that display tumor-specific targeting receptors e. In an interesting study, metastatic-Trap m-tarp was manufactured using exosomes embedded on a three-dimensional platform as a trap favorable secondary site to lure metastatic cells. For this, exosomes purified from the ascitic fluid of ovarian cancer patients were validated as intermediaries of tumor cell attachment.

Transplantation of the device into the peritoneal cavity of mice resulted in the capturing of ovarian metastatic cells and significantly improved survival outcomes by disrupting the crosstalk between metastatic cells and their environment de la Fuente et al. On the bright side, the potential of exosomes as natural and non-toxic agents vectors to induce long-term changes in the receipt cells was further translated into the gene therapy as an alternative to the time-consuming and laborious gene cloning as well as for targeted functionalized exosomes and controlled drug delivery.

Indeed, the evidence for HGT related to the transfer of mitochondria has changed the previously accepted paradigms regarding the role of anaerobic glycolysis in cancer cell metabolism.

Although glycolytic metabolism is recognized as the key hallmark of many cancer cells, tumor cells also need oxidative phosphorylation OXPHOS to meet their pathophysiological demands.

On the contrary to the previous fact suggested by Warburg that defects in mitochondria are causative to cancer initiation, some cancer cells retain OXPHOS capacity with no clear respiratory defects Frezza and Gottlieb, ; Jose et al. Respiration is key for cancer cell formation, proliferation, progression, and metastasis Viale et al.

Surprisingly, cancer cells deprived of mtDNA can restore their respiration potential through a rare phenomenon which is regulated by HGT involving the transfer not of mtDNA but of whole mitochondria Tan et al. Results from an invaluable study revealed that mtDNA-deficient tumor display delays in tumor formation potential compared to their normal counterpart.

It also showed that progression was associated with respiration recovery and acquiring mtDNA from the host. Further studies showed that efficient tumor formation, recovery of mitochondrial respiration, and mtDNA acquisition occurs via trafficking of whole mitochondria between mammalian cells in vivo Dong et al.

As a therapeutic strategy, mitochondria transplantation is demonstrated to improve antitumor activity and reduce chemoresistance and mitochondrial dynamics in breast cancer in vitro Chang et al. Since the genetic remodeling of a single organism is not enough to meet this requirement, HGT has emerged as an effective approach to provide such a survival advantage. The appearance of phenotypic changes can be immediate e. Horizontal gene transfer acts as a double-edged sword: although it fuels innovation and diversity in nature, now, its effects function against the survival benefit in nature, especially in humans.

For one, the dawn of the post-antibiotic area is highly predicted as a consequence of HGT in the future, at a time point in which the bacteria will no longer respond to antibiotics. Equally, in the context of other diseases, such as cancer, HGT not only promotes the development of the clonal population of cells capable of tumorgenesis, it also sparks tumor cell heterogeneity and the emergence of multi-drug resistance Dianat-Moghadam et al.

Such survival advantage to tumors is mediated, partly, by the newly discovered HGT mediators in the eukaryotes. DNA from apparently dead tumor cells, called apoptotic bodies, can be transferred to living tumor cells, as naked, in complex with other biomaterials or being packed into the EVs. Organotypic metastasis, which refers to the tendency of tumors to seed in selective and preferred organs, has recently been shown to be regulated by exosomes.

Indeed, the expression of specific surface receptors on exosomes is shown to prepare secondary organs for tumor metastasis. And that disrupting these interactions can selectively avoid metastatic outbreaks in several mice models Hoshino et al. Accordingly, the most important matter about HGT is to understand its transmission mechanism s , which, in turn, will provide many advantages and opportunities.

For example, instead of focusing on the development of new antibiotics, the horizontal transmission mechanism in bacteria will be considered as a therapeutic target.

Given that the process for the development of new antibiotics is time-consuming and expensive, disruption of HGT in bacteria populations, using, for example, the CRISPR-Cas9 system, can disconnect genetic exchange among bacteria. Thus, not only can the development of antibiotic drug resistance be prevented, but inter- and intra-species transmission of virulence factors can be reduced as well. This is of paramount importance given the ever-increasing cases of acquired resistance to a wide range of routinely- and clinically used antibiotics.

From another angle, a comprehensive understanding of HGT mediators will offer a great benefit to genetic engineering. Given the high costs and low efficiency of current gene therapy tools, recognition of HGT mechanisms can lead to the development of more efficient and cheaper gene therapy methods, for treatment of postnatal genetic diseases such as those related to a specific enzyme deficiency metabolic disorders or even for the treatment of cancer.

Thus, it can predict the recipient bacteria that will become resistant to specific antibiotics. As the target host is already predicted, a combination modality can be highly effective to monitor resistance to the newly introduced antibiotics in the clinic. Equally, machine learning can be applied for the prediction of mobile elements movement in the human genome. Half of the human genome is composed of inserted sequences from other organisms, of which only transposons have the capability of jumping and transferring gene fragments in the eukaryotic DNA.

As the role of TEs is well established in the pathogenesis of multifactorial diseases, such as cancer and neurodegenerative disease, a machine learning approach can spot the next location of jumping elements in the human genome. Once the new jumping site is recognized, then one can predict the good or bad consequence of transposon insertion.

Finally, the more recent clinically important mediators of HGT among eukaryotic cells are exosomes, cfDNA, and apoptotic bodies, through which distant cancer cells can communicate together. Thus, it allows the clinicians to plan the most suitable drug regimens based on disease state and adopt a timely intervention to control the disease and achieve desirable therapeutic effects Baghban et al.

Thus, horizontal transfer mediators may be the next generation point-of-care diagnostic, prognostic, and therapeutic tools to predict, cure, and prevent various human-related maladies, in particular cancer.

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It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Materials and Methods. Results and Discussion. Literature Cited. Ravi Jain , Ravi Jain. E-mail: lake mbi. Oxford Academic. Google Scholar. Maria C. Jonathan E. James A. Select Format Select format.

Permissions Icon Permissions. Abstract Horizontal gene transfer HGT spreads genetic diversity by moving genes across species boundaries. William Martin, Associate Editor. Open in new tab Download slide. Issue Section:. Download all slides. View Metrics.



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