For foreign DNA to make it into a eukaryotic cell’s genome, DNA must first enter the cell, then cross the nuclear envelope, and finally insert itself into the genome. Below are a number of proposed mechanisms by which this may unfold.
In addition to inserting their own genetic material into their hosts, viruses can pick up and carry genes from the various species they infect and may therefore serve as ferries for HGT. One 2018 study showed that geminiviruses can move host genes from one plant to another.
These small bubbles of membrane are known to transport molecules between cells and can carry chunks of DNA. In lab studies, extracellular vesicles have been implicated in the introduction of foreign DNA into cultured cells, including the integration of cow DNA from the fetal bovine serum in culture media into mouse cells.
Microbial eukaryotes that engage in phagotrophy to consume microbes might receive gene transfers from the DNA in their meals. Evidence for this idea is seen in the numerous reported laterally transferred genes in phagotrophic protists.
Endosymbionts or endoparasites
Studies are accumulating that suggest the rate of gene transfers is higher to and from cytoplasm-dwelling species. Malaria parasites, for instance, take in and express human DNA when living inside blood cells. And bacteria that live inside insect cells have transferred numerous genes to their hosts, allowing the parasites to survive with extremely small genomes.
Although the mechanisms are unclear, cells are known to pull in external DNA molecules under the right conditions. That means DNA in the environment—from shed skin, mucus, spawned gametes, or other sources—may find its own way into cells and thus act as source material for transfers, as is suspected in the transfer of an ice binding protein between arctic fishes.
Viruses, especially DNA viruses, are often able to sneak genetic material into their host’s nucleus. The 2018 study on geminiviruses found that genes acquired from one host were transcribed in another after infection, indicating the viral minicircles containing host DNA made it into the new host’s nucleus.
Studies have found that DNA injected into the cytoplasm can make its way into the nucleus. One way this can occur is through the association with proteins that have nuclear localization signals, such as transcription factors or histones; the proteins essentially drag the DNA with them as they’re ferried through the nuclear pores. Other, as of yet undescribed mechanisms likely exist.
Many kinds of viruses, including retroviruses, have can add DNA to chromosomes—hence their use in certain transfection methods. However, it has not been conclusively shown that wild viruses have inserted host-derived genes into other hosts’ genomes.
DNA in the nucleus may get incorporated during repair processes. For instance, when DNA breaks are induced using CRISPR/Cas9, researchers have found that unintentional additions of DNA can occur.
Once foreign DNA is in the nucleus, it may get incorporated into the genome with the help of transposons, which excise and insert themselves through well-documented mechanisms. Indeed, recently transferred sequences are often flanked by such jumping genes.
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