Researchers fondly call the roundworm Caenorhabditis elegans “the worm” because of its widespread use in research to understand neuronal and molecular biology. It was the first multicellular organism to have its full genome sequenced and neural wiring mapped. C. elegans grows within 3-5 days from a fertilised egg to a millimetre-long adult, and it has informed profound insights into the human body, as well as biology more broadly.
On March 28, researchers from Princeton University in the U.S. reported that after C. elegans worms ate a disease-causing strain of bacteria, its children inherited the ‘knowledge’ to avoid making the same mistake — up to four generations. Their findings were published in the journal PLoS Genetics.
Given the mechanism by which this transmission occurs, the study raises questions about whether humans could have the same ability.
Message in a bottle
Pseudomonas vranovensis is a disease-causing bacterium found in C. elegans’s natural environment.
The researchers found that P. vranovensis makes a small RNA molecule called sRNA. When the worms ingest this strain, they also take in the sRNA. The sRNA then altered the worm’s feeding behaviour such that, from that point on, the worms ‘know’ to avoid feeding on this bacterium and save themselves from getting sick.
Remarkably, this learned avoidance behaviour was found to be transmitted to the trained worm’s progeny, grand-progeny, great-grand progeny, and great-great-grand progeny. The ability decayed only from the fifth generation.
The same team of researchers had previously discovered this trans-generational ability in C. elegans worms against P. aeruginosa bacteria (which also cause disease in humans). In the new study, they were able to confirm C. elegans worms in the wild had the same ability.
Understanding RNA, large and small
A DNA molecule is like a big ladder. Its two side rails, or strands, are made of a long series of alternating units of phosphate 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). The As and Cs on one strand are bonded with Ts and Cs on the other by hydrogen bonds. These bonds form the rungs that hold the strands together.
A single P. vranovensis bacterium has 6-7 million rungs in its DNA, coding for about 5,500 genes. A gene is a segment of a few thousand base-pairs of the DNA molecule. Every gene is instructions that tell a cell how to make a protein.
In contrast to DNA, the RNA molecule is like a half-ladder or a comb. Its spine is made up 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 jut out from the strand like the comb’s tines. A cell copies the sequence of As, Ts, Cs, and Gs in a gene in the DNA into the sequence of Us, As, Gs, and Cs in an RNA molecule. This RNA is called the messenger (mRNA). The length of this mRNA is comparable to that of the gene from which it is derived. The mRNA moves to structures called ribosomes, where the cell assembles the corresponding protein.
Diet control
But not all genes encode mRNAs and proteins. The end product of some genes, especially small genes that are only about a tenth as long (~100-200 rungs), is sRNA. These sRNA bind to other proteins and RNAs, and either enhance or reduce the expression of other genes.
The Princeton University researchers showed that a C. elegans worm took up a 124-tine sRNA from an ingested P. vranovensis. This sRNA reduced the expression of a gene in the worm called maco-1, which plays an important neurological role. As it happens, maco-1 is also found in humans.
In the laboratory, the researchers reared C. elegans worms on a diet of Escherichia coli bacteria. When the researchers engineered the E. coli to express the P. vranovensis sRNA and fed them to the worms, the worms learned to avoid the pathogenic strains of P. vranovensis. When these worms had children, the latter also had the ability to avoid pathogenic P. vranovensis.
Good ‘memory loss’
Another Pseudomonas bacterium, P. mendocina, is also present in the worm’s habitat but it doesn’t cause disease. Instead, P. mendocina is a source of nutrition. C. elegans worms trained to avoid the pathogenic P. vranovensis strain avoided feeding on the non-pathogenic P. mendocina as well. The researchers have speculated that this is perhaps why the ‘loss of memory’ happens around the fifth generation — so they can re-remember the advantage of consuming P. mendocina.
The sRNA that triggered learned avoidance behaviour came initially from the bacteria and was taken up by the worm that fed on them. Thereafter, the sRNA was maintained in the worms’ bodies, transmitted to their descendants, and maintained in them. This happened through a mechanism called RNA interference — which scientists first discovered by studying C. elegans worms.
Food for thought
In fact, discoveries based on studying C. elegans were recognised by Nobel Prizes in 2002, 2006, and 2008. This tiny worm has played an outsized role in the advancement of scientific and medical research.
For example, a gene that triggers a process during C. elegans’s development has been found in the human genome, and mutations in it have been associated with limb deformities.
So a question arises: whether our bodies can also take up sRNA molecules from the microbes in our gut, mouth or vagina, and whether they can modify our behaviour, and possibly the behaviour of our children and later generations.
D.P. Kasbekar is a retired scientist.
