Ocean’s Genetic Messengers: Tiny Vesicles Redefine Cell Communication

Extracellular vesicles significantly contribute more to horizontal gene transfer in oceans than previously thought.

The oceans are teeming with microorganisms engaging in a dynamic exchange of genetic material. This process, known as horizontal gene transfer (HGT), plays a pivotal role in the evolution of numerous speciesA species is a group of living organisms that share a set of common characteristics and are able to breed and produce fertile offspring. The concept of a species is important in biology as it is used to classify and organize the diversity of life. There are different ways to define a species, but the most widely accepted one is the biological species concept, which defines a species as a group of organisms that can interbreed and produce viable offspring in nature. This definition is widely used in evolutionary biology and ecology to identify and classify living organisms.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>species and is a key factor in the spread of antibiotic resistance among bacteria. Traditionally, it was believed that this gene exchange occurred mainly through direct cell contacts, free-floating DNADNA, or deoxyribonucleic acid, is a molecule composed of two long strands of nucleotides that coil around each other to form a double helix. It is the hereditary material in humans and almost all other organisms that carries genetic instructions for development, functioning, growth, and reproduction. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>DNA, or viruses.

A study led by Susanne Erdmann from the Max Planck Institute for Marine Microbiology in Bremen now shows that so-called extracellular vesicles are also very important for the transfer of genetic information in the sea and thus for the life of its smallest inhabitants.

Viruses, GTAs, EVs: tiny and numerous

Most viruses are tiny. Up to 10 million of them can be found in every drop of seawater. They can not only pack up their own genetic material (their genome) but also parts of their host’s DNA – i.e. the DNA of the organism they have infected – and transport it into other cells.

Studying viruses is challenging. Seawater samples have to be filtered through filters with a pore size of only 0.2 µm (which is about 300 times less than the thickness of a human hair) to separate the viruses from the cells. In addition to viruses, these filtered samples also contain so-called gene transfer agents (GTAs) and extracellular vesicles (EVs).

For this study, the researchers from the Max Planck Institute in Bremen also collected water samples off the North Sea Island of Helgoland. Credit: Silvia Vidal / Max Planck Institute for Marine Microbiology

GTAs are virusA virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>virus-like particles that exclusively package host DNA and EVs are small vesicles enveloped by a membrane that detach from the cell surface of the host. These EVs can contain a variety of molecules. In addition to enzymes, nutrients, and RNARibonucleic acid (RNA) is a polymeric molecule similar to DNA that is essential in various biological roles in coding, decoding, regulation and expression of genes. Both are nucleic acids, but unlike DNA, RNA is single-stranded. An RNA strand has a backbone made of alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four bases—adenine (A), uracil (U), cytosine (C), or guanine (G). Different types of RNA exist in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>RNA, they often transport fragments of DNA.

EVs are prolific transporters of genetic material

Erdmann and her team have now shown that, other than previously assumed, there is a lot of host DNA in the filtered seawater samples that is not transported by viruses. Proving this was extremely complicated. “After sequencing, i.e. reading out the host DNA, we can no longer recognize how it got into our sample,” explains Erdmann, head of the Max Planck Research Group Archaea Virology at the Max Planck Institute in Bremen.

“There is no feature to assign a sequence to a specific transport mechanism.”

To solve this problem, the researchers used a trick. In a first step, they assigned each DNA sequence to a host from which it originally stems. Then they determined a main transport mechanism for each host as far as possible – i.e. by viruses, GTAs or EVs. This enabled them to assign a potential transport mechanism to a specific DNA sequence.

“The result was surprising: Apparently, a large proportion of the DNA was not transported via classical routes, but via extracellular vesicles,” says Erdmann.

So much more than waste – in the ocean and beyond

“Extracellular vesicles were long regarded as cellular waste. Only in the last fifteen years, scientists were able to show their various functions for the cell. Our study clearly highlights the fundamental role that EVs play for the exchange of genetic material between cells,” explains Dominik Lücking, a Ph.D. student in Erdmann’s group and first author of the study, which has now been published in the journal ISME Communications.

Thus, the authors suggest changing terminology: “Traditionally, we are talking of a virome, a metagenome enriched with viruses, when extracting and sequencing the DNA from the 0.2 µm fraction,” says Lücking. “However, that way we are missing out on the variety of the other, non-virus-like particles in this fraction, such as EVs. Thus, we suggest calling this fraction ‘protected extracellular DNA’, or peDNA.”

The study presented here lays the foundation for future research on peDNA across all ecosystems, in the ocean and beyond. “The new nomenclature will enable us to talk more clearly about the mechanisms and processes not covered by the term virome,” says Erdmann.

Future research can use this study as a guideline to assess the role of extracellular vesicles in other environments, such as soil and freshwater systems or the human gut. „In view of the significance of horizontal gene transfer in many ecosystems, we are very sure that there are quite a few more surprises on the way ahead of us,“ Erdmann concludes.

Reference: “Extracellular vesicles are the main contributor to the non-viral protected extracellular sequence space” by Dominik Lücking, Coraline Mercier, Tomas Alarcón-Schumacher and Susanne Erdmann, 17 October 2023, ISME Communications.
DOI: 10.1038/s43705-023-00317-6