Don't eat it, great-great-grandchildren!
Nematodes have memorized pathogenic bacteria for four generations
Vera Mukhina, N+1
Epigenetic memory allowed the roundworms Caenorhabditis elegans to remember the harm from the bacterium Pseudomonas aeruginosa so well that their descendants continued to bypass them for four generations. The results of the study published in the journal Cell (Moore et al., Piwi/PRG-1 Argonaute and TGF-β Mediate Transgenerational Learned Pathogenic Avoidance) demonstrated that this is due to the activity of non-coding piRNAs and interacting proteins in worm neurons.
Despite the conservatism of the DNA sequence itself, organisms are able to quickly change the epigenetic settings of the genome in order to quickly adapt to external events. These settings can be saved for different periods of time, and in some cases, even inherited. For example, stress or diet affect the appearance and predisposition of offspring to diseases. Over the past few years, quite a lot of such examples have accumulated in the scientific literature, but the possibility of transmitting complex behavioral patterns related to memory and learning has been studied very poorly. New results of a group of researchers from Princeton says that this is possible: using the example of nematodes, they have analyzed the mechanism of occurrence and inheritance of such a pattern.
In nature, C. elegans worms often live in the neighborhood of bacteria, some of which can serve as food, and others, such as Pseudomonas aeruginosa, are pathogens. It is known that if you put these bacteria and worms together, P. aeruginosa initially attracts nematodes, but then, within a few hours, the worms learn to avoid them.
To understand how the mechanism of memorization works, Rebecca Moore and her colleagues compared the transcription profiles of nematodes of parents and their descendants who interacted with Pseudomonas aeruginosa or with the bacterium E. coli (control condition). The main differences were found in neurons; in particular, worms familiar with P. aeruginosa and their "vindictive" offspring showed increased activity of daf-7 – ligand of the TGF-β protein in neurons that are responsible for avoiding pathogenic bacteria. It turned out that blocking this gene in the offspring of nematodes "erases" their memory and Pseudomonas aeruginosa sticks become attractive to them again.
The control of gene activity, as scientists have found out, occurs largely with the help of modifications of histones, protein complexes on which DNA is wound. Depending on them, the density of DNA packaging changes and, accordingly, its availability for proteins involved in RNA synthesis. In turn, histone modifications may be due to the interaction of argonaut proteins and non-coding piRNAs. It was this way of regulating the activity of genes that turned out to be critical for the formation of epigenetic memory of nematodes: turning off the genes of this pathway deprived animals of the ability to transmit the memory of harmful bacteria to offspring.
A drawing from an article in Cell.
Researchers have thus confirmed that worms are able to transmit such a "memory" to their children so that interest in these pathogens reappears only in the fifth generation. At the same time, the nematodes did not remember other, less dangerous bacteria.
Another article on a similar topic was published in the same issue of Cell. In it, Rachel Posner and her colleagues also showed that changes in preferences in chemotaxis can be transmitted through several generations and regulated using small RNAs. They demonstrated that a change in the activity of the regulatory gene RDE4 in neurons causes a response in the cells of the nematode gonads: the number of small RNAs increases there and the activity of the genes regulated by them decreases proportionally. Among the latter was the saeg2 gene, which plays an important role in the stress chemotaxis of these animals. These changes were inherited over three generations: the neural activity of RDE4 in ancestral nematodes affected the chemotaxis of their great-grandchildren.
An interesting mechanism underlying the behavior of nematodes was recently discovered by another group of researchers. Usually worms are not averse to eating the larvae of other nematodes, but they do not touch their offspring. It turned out that they recognize their own thanks to a signaling protein located on the cuticle of worms.
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