Researchers affectionately refer to the roundworm Caenorhabditis elegans as “the worm.” This is because it is widely used in research to understand neurobiology and molecular biology. It was the first multicellular organism to have its complete genome sequenced and its neural wiring mapped. C. elegans grows from a fertilized egg to a millimeter-long adult within three to five days, providing deep insights into the human body and broader biology.
On March 28, researchers at Princeton University in the US found that after C. elegans worms eat a disease-causing strain of bacteria, their children acquire up to four generations of “knowledge” to avoid the same mistakes. It was reported that it was inherited over the years. Their findings were published in the journal PLoS Genetics.
Given the mechanism by which this transfer occurs, this study raises the question of whether humans can have the same ability.
message in a bottle
Pseudomonas branovensis is a disease-causing bacterium found in C. elegans' natural environment.
Researchers discovered that P. vranovensis makes small RNA molecules called sRNAs. When the worms ingest this strain, they also ingest the sRNA. The sRNA then changed the worm's feeding behavior, and from that point on, the worm “knew” to avoid eating this bacterium and avoid getting sick.
Remarkably, this learned avoidance behavior was found to be transmitted to the offspring, great-grandchildren, great-great-grandchildren, and great-great-grandchildren of the trained C. elegans. Only from the fifth generation onwards did their abilities decline.
The same research team had previously discovered the nematode's transgenerational ability to fight Pseudomonas aeruginosa (which also causes disease in humans). A new study confirms that wild worms have the same ability.
Understanding large and small RNA
The DNA molecule is like a big ladder. Its two side rails, or strands, are composed of long series of alternating units of phosphate molecules and the sugar deoxyribose molecules. Each sugar unit is attached to one of four chemical bases: adenine (A), cytosine (C), guanine (G), and thymine (T). As and Cs in one chain are combined with Ts and Cs in the other chain by hydrogen bonds. These bonds form rungs that hold the strands together.
The DNA of a single P. vranovensis bacterium has 6 to 7 million rungs and encodes approximately 5,500 genes. Genes are segments of several thousand base pairs of DNA molecules. All genes are instructions that tell cells how to make proteins.
In contrast to DNA, RNA molecules are like half-ladders or combs. Its spine is composed of alternating units of phosphate and the sugar ribose. Each ribose molecule is attached to one of four bases: A, C, G, or uridine (U), which protrude from the chain like the teeth of a comb. The cell copies the As, Ts, Cs, and Gs sequences of the gene in the DNA to the Us, As, Gs, and Cs sequences of the RNA molecule. This RNA is called messenger (mRNA). The length of this mRNA is comparable to the length of the gene from which it is derived. The mRNA travels to structures called ribosomes, where the cell assembles the corresponding protein.
meal management
However, not all genes code for mRNA or proteins. The final product of some genes, especially small genes that are only about a tenth of a length (about 100 to 200 rungs), is an sRNA. These sRNAs bind to other proteins and RNAs, increasing or decreasing the expression of other genes.
Researchers at Princeton University showed that C. elegans worms take up 124 sRNAs from ingested P. vranovensis. This sRNA decreased the expression of a gene in the worm called maco-1, which plays an important neurological role. Coincidentally, maco-1 is also present in humans.
The researchers reared worms in the lab on E. coli. When the researchers engineered E. coli to express P. vranovensis sRNA and fed it to worms, the worms learned to avoid the pathogenic strain of P. vranovensis. When these nematodes gave birth to offspring, the latter also had the ability to evade pathogenic P. vranovensis.
Good “amnesia”
Another Pseudomonas bacterium, P. mendocina, is also present in the insect's habitat, but it does not cause disease. Instead, P. mendocina serves as a nutritional source. C. elegans nematodes trained to avoid the pathogenic P. vranovensis strain also avoided eating the non-pathogenic P. mendocina. Researchers speculate that this is probably why “amnesia” occurs around the fifth generation. So we can once again remember the benefits of consuming P. mendocina.
sRNAs that trigger learned avoidance behavior were originally derived from bacteria and taken up by nematodes that feed on bacteria. The sRNA is then maintained within the worm's body, transmitted to its offspring, and maintained within the worm. This happened through a mechanism called RNA interference. This mechanism was first discovered by the scientist in his study of the C. elegans nematode.
food for thought
In fact, discoveries based on C. elegans research were recognized with Nobel Prizes in 2002, 2006, and 2008. This tiny nematode has played a huge role in advancing scientific and medical research.
For example, a gene that triggers a process during development in C. elegans was discovered in the human genome, and mutations in it were found to be associated with limb deformities.
That begs the question. Can our bodies also take up sRNA molecules from the microbes in our gut, mouth and vagina, and whether they can change our behavior and perhaps the behavior of our children and future generations? The question is, can it be done?
DP Kasbekar is a former scientist.
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