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Horizontal gene transfer in eukaryotes: A biological phenomenon with unknown molecular mechanisms but accumulating DNA evidence
2024 Volume 89 Issue 2 Pages 85-88
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2024 Volume 89 Issue 2 Pages 85-88
Horizontal gene transfer (HGT) between different organisms is one of the primary forces driving evolution. Recent advances in sequencing and genome analysis technologies have enabled the discovery of evidence for HGT from a wide range of eukaryotic genomes. It is well established that parasitic or symbiotic organisms can transfer genes to their hosts via viruses or transposons. Furthermore, there have been reports of horizontal transfer from one cell to another by apoptotic vesicles or exosomes. This suggests that they may play a role in the onset and recurrence of human diseases, including cancer and metabolic diseases. In this review, we present newly reported cases of HGT in eukaryotic organisms and discuss future research trends.
In the majority of cases, the genetic information of an organism is transmitted from parents to offspring via reproduction. This phenomenon is referred to as vertical gene transfer. In contrast, the phenomenon of horizontal gene transfer (HGT) refers to the transfer of genes between individuals or different organisms that are not descendants. It is widely believed that the diverse evolution of organisms has been possible because new traits could be acquired through HGT from different organisms (Keeling and Palmer 2008). However, the majority of knowledge about HGT originates from prokaryotes (Etten and Bhattacharya 2020). This is because eukaryotic organisms possess larger and more complex genomes than prokaryotes, which makes genome analysis difficult (Keeling 2024). Nevertheless, recent advances in sequencing and genome analysis technologies have enabled the analysis of eukaryotic organisms. Currently, evidence of HGT can be identified in a diverse range of species, including protists, plants, and vertebrates. Here, we introduce the emerging trends in future research while presenting case studies of HGT in eukaryotic organisms from previous studies.
The initial experiment to observe HGT was likely conducted by Griffith (1928) with Streptococcus pneumoniae bacteria. Nevertheless, the specific agent responsible for the transformation of inactivated Streptococcus pneumoniae pathogenic S-type bacteria into non-pathogenic R-type bacteria remained unknown. The substance was identified as DNA by Avery et al. (1944). In the 1950s, it was proposed that bacterial conjugation and transformation were phenomena of HGT (Tatum and Lederberg 1947; Zinder and Lederberg 1952). With the remarkable improvement in genomic analysis technologies, molecular biology techniques directly targeting DNA became integrated into research on HGT around the 1990s (Arauchi et al. 2014). The advent of next-generation sequencers in 2005 enabled the rapid revelation of genomic sequences of eukaryotes (Fujiwara et al. 2021). These next-generation sequencers can decode approximately 1 billion bases in a single run, surpassing the complexity of genomes of bacteria and facilitating the decoding of genomic sequences of eukaryotes with ease (Arauchi et al. 2014). Thereby technological advancements have enabled the discovery of traces of HGT from genomic sequences even in eukaryotes, where analysis was previously difficult.
In eukaryotic organisms, HGT has occurred from closely associated prokaryotes through symbiosis or ingestion. The following section will provide specific examples of HGT, categorized by the triggers for this process. The first is an example of HGT that has occurred in prokaryotes that are closely associated with symbiosis or ingestion. The flagellate Trichonympha agilis, a symbiont of Reticulitermes speratus, has been found to harbor two bacterial species, whose genome fragments are horizontally transmitted to the host flagellate genome (Fig. 1A) (Sato et al. 2014). A similar phenomenon has been observed in the whitefly (Bemisia tabaci), where biotin biosynthesis-related genes from the symbiotic bacterium Hamiltonella have been horizontally transferred to the whitefly genome (Fig. 1B). It has been demonstrated that the expression of horizontally transferred biotin genes increases in whiteflies when Hamiltonella is removed (Ren et al. 2020). Another example of feeding is the carnivorous beetle ladybird. It is hypothesized that the cell wall hydrolase (cwh) of bacteria symbiotic to the insect was acquired by ladybird beetles during the process of feeding on other insects (Li et al. 2021). This acquisition has been associated with improved immunity, leading to diversification within the carnivorous ladybird beetle lineage (Fig. 1C).
The second is an example of HGT occurring when environmental stresses cause DNA double-strand breaks. The freshwater rotifer undergoes asexual reproduction but is capable of exchanging DNA horizontally within and between species. They can induce double-stranded DNA breaks due to desiccation and subsequently incorporate foreign DNA during the process of chromosome repair (Hespeels et al. 2014; Eyres et al. 2015). This process facilitates their diverse evolution and adaptation to the environment, as they acquire various genes from external sources even during asexual reproduction (Fig. 1D).
The third is an example of HGT mediated by vectors such as viruses (Fig. 1E). The whitefly has been suggested to acquire the BtPMaT1 gene, a plant detoxification gene, through plant ingestion and the action of viruses (Xia et al. 2021). Many plants release phenolic glycosides into their sap as a defensive mechanism against sap-sucking pests. However, these phenolic glycosides are not only harmful to pests but also to the plants themselves. Therefore, plants possess the BtPMaT1 gene to detoxify the toxins they secrete. It is believed that the whitefly gained resistance to plant toxins by acquiring the BtPMaT1 gene (Xia et al. 2021).
The fourth is an example where HGT has occurred through parasitism rather than symbiosis. For instance, Striga hermonthica, a member of the true dicotyledons that is widely distributed in Africa, parasitizes the roots of monocotyledons such as maize and sorghum, extracting water and nutrients. Extensive analysis of expressed sequence tags (ESTs) from Striga revealed the presence of a gene, ShContig9483, which exhibited high similarity to genes in the maize genome (Yoshida et al. 2010). The formation of a dendritic structure, known as haustoria, by parasitic plants is believed to facilitate the movement of nutrients, water, and even mRNA between the parasitic plant and the host’s vascular system and cell-to-cell connections, leading to HGT (Fig. 1F) (Kim et al. 2014; Wickell and Li 2020). Another intriguing example is provided by the parasitic worm of the praying mantis, the wireworm. The wireworm (Chordodes fukuii) is known to induce the mantis (Tenodera angustipennis) to enter water, its oviposition site (Obayashi et al. 2021). Transcriptome analysis of the wireworm and its host mantis revealed that many of the genes showing altered expression levels in the wireworm were highly similar at the nucleotide sequence level to genes in the mantis (Fig. 1G) (Mishina et al. 2023). Some of these genes have functions related to manipulating mantis behavior, suggesting that the wireworm may control its host using genes acquired from the mantis (Mishina et al. 2023). In vertebrates, it has been demonstrated that a retrotransposon designated BovB has undergone horizontal transfer from snakes to frogs (Fig. 1H) (Kambayashi et al. 2022). Furthermore, BovB was identified in leeches that were blood-sucking on humans in Madagascar, suggesting the occurrence of horizontal transfer among vertebrates other than snakes and frogs (Fig. 1I) (Kambayashi et al. 2022).
Consequently, HGT in eukaryotes occurs across a diverse range of species, with a multitude of potential triggers and acquired genes. Nevertheless, the precise mechanisms remain to be fully elucidated. Why do organisms engage in HGT? One reason is the rapid acquisition of beneficial genes. The emergence of new beneficial genes is likely rare, and acquiring genes from other organisms is often much quicker than waiting for independent evolution (Vogan and Higgs 2011). Therefore, it is believed that HGT occurs among various organisms with different traits.
However, HGT also presents several potential drawbacks. These include acquired sequences residing in non-coding regions devoid of genetic information, duplication of genes already presents within the cell, or functioning ineffectively in the presence of other genes not contained in the host cell (Vogan and Higgs 2011). Additionally, even if newly acquired genes are expressed, they may be harmful to the host if their gene products lack useful functions (Vogan and Higgs 2011). An example of HGT becoming detrimental is seen in cell carcinogenesis. Most of normal mammalian cells have the ability to uptake substances from their surrounding environment. It was demonstrated that when apoptotic vesicles derived from cancerous cells are taken up, genetic information related to cancer is horizontally transferred, leading to the carcinogenesis of normal cells (Bergsmedh et al. 2001). It has been suggested that HGT mediated by elements such as exosomes and mobile genetic elements like transposons, which are known for their ability to move genes, is involved in the onset and recurrence of various human-related conditions including genetic disorders, metabolic diseases, and neurodegenerative diseases (Emamalipour et al. 2020). Thus, HGT can be both beneficial and detrimental to the host.
Currently, insights into HGT from various organisms are anticipated for applications in agriculture and medicine. Firstly, in agriculture, a novel pest control method utilizing RNA interference (RNAi) to suppress gene expression is being explored (Ortolá and Daròs 2024). Indeed, when exposed to double-stranded RNA specific to the detoxification gene BtPMaT1, aphids resistant to plant toxins were unable to detoxify the poison via RNAi (Xia et al. 2021). Given the prevalence of pest damage across many crops, the development of transgenic plants inducing RNAi with insecticidal effects is gaining attention (Feng et al. 2023). As RNAi functions as a natural mechanism for gene expression suppression, it is believed to offer an environmentally friendly approach to pest control.
In the medical field, there is a growing interest in exosomes, which transport substances such as RNA and proteins to cells. Research is underway to utilize exosomes for biomarker retrieval and as carriers for delivering drugs to specific cells, potentially establishing novel therapeutic approaches (Valcz et al. 2022). Moreover, unexpected HGT can also occur with CRISPR-Cas9 genome editing (Liang et al. 2023). Recent studies have revealed that HGT mediated by exosomes occurs during the process of repairing DNA double-strand breaks (DSBs) in genome editing and serum-derived bovine and goat DNA in the culture medium were incorporated into the genome of the host after genome editing (Ono et al. 2019). The repair of DSB typically occurs via two mechanisms: non-homologous end joining (NHEJ) or homologous recombination. NHEJ carries a risk of unintended insertion of DNA sequences to DSB sites. Although the probability of this is very low, it was necessary to pay attention to the risk of HGT due to the incorporation of heterologous DNA during NHEJ repair to the DSB created by genome editing. Recently, researchers have developed the novel genome editing technologies without DSB including base editing with activation-induced cytidine deaminase and nickase (Komor et al. 2016; Nishida et al. 2016), and prime editing with reverse transcriptase (Chen and Liu 2023), there is no issue with HGT via NHEJ.
With the advent of more sophisticated genome analysis techniques, HGT has been confirmed in a multitude of eukaryotes. However, the detailed molecular mechanisms underlying how genes are horizontally transferred remain elusive. Future research could lead to reduce or avoid the risk of unintended DNA sequence transfer and contribute to the development of breakthrough technologies to introduce heterologous genes into the genome.
This work was supported by grants from MXT/JSPS KAKENHI (20H03297 and 22H00415), JST CREST (JPMJCR20S6), GteX (JPMJGX23B0), and ASPIRE to S.M.
