Genome complexity: epigenetics in action (Introduction)

by David Turell @, Monday, June 10, 2019, 19:27 (102 days ago) @ David Turell

C. elegans can transfer avoidance for four generations, and then it disappears:

"Princeton University researchers have discovered that learned behaviors can be inherited for multiple generations in C. elegans, transmitted from parent to progeny via eggs and sperm cells.


"'In their natural environment, worms come into contact with many different bacterial species. Some of these are nutritious food sources, while others will infect and kill them," said Murphy, a professor in Princeton's Department of Molecular Biology and the Lewis-Sigler Institute for Integrative Genomics. "Worms are initially attracted to the pathogen Pseudomonas aeruginosa, but upon infection, they learn to avoid it. Otherwise they will die within a few days."


"They found that when mother worms learned to avoid pathogenic P. aeruginosa, their progeny also knew to avoid the bacteria. The natural attraction of offspring to Pseudomonas was overridden even though they had never previously encountered the pathogen. Remarkably, this inherited aversive behavior lasted for four generations, but in the fifth generation the worms were once again attracted to Pseudomonas. In another surprise, the researchers observed that inheritance of learned avoidance was not universal for all pathogenic bacteria; although mother worms could learn to avoid the pathogenic bacterium Serratia marcescens, which is less abundant than Pseudomonas in C. elegans' environment, this aversion was not passed down to offspring. Intrigued, the researchers set out to explore what controls transmission of P. aeruginosa avoidance behavior across generations.

"The authors showed that C. elegans mothers must actually become ill from ingesting P. aeruginosa in order to transmit avoidance to future generations; exposure to odors emitted by the pathogen wasn't sufficient to provoke avoidance. Nonetheless, neuronal sensory pathways are important for inherited avoidance, because avoidance behavior in both mothers and their progeny was associated with upregulated expression of several neuronally-associated genes. Among these, elevated expression of the TGF-β ligand daf -7 in mothers was needed for progeny to inherit pathogen aversion. Moore and her colleagues found that daf-7 expression in a certain type of sensory neuron, ASI neurons, correlated strongly with inherited avoidance behavior.

"'The process of inheriting this learned avoidance [also] requires the activity of small RNAs called piRNA," Murphy said. piRNAs have been implicated in other transgenerational epigenetic inheritance pathways in C. elegans, where they're thought to silence gene expression and indirectly regulate DNA packing. The researchers found that the piRNA-associated protein PRG-1, while not necessary for C. elegans mothers to learn avoidance of P. aeruginosa, was required for increased daf-7 expression in progeny, and for their inherited avoidance behavior. Whether piRNAs and PRG-1 operate primarily in the mother, the progeny, or both to promote inheritance of avoidance behavior isn't yet known.

"Importantly, expression of daf-7 remains elevated in the ASI neurons of progeny for four generations, then returns to basal levels in the fifth generation, which is when the inherited avoidance behavior also disappears. As Murphy points out, although inheritance of avoidance behavior provides a survival advantage, it's also necessary for this avoidance behavior to eventually go away. That's because P. aeruginosa is only pathogenic at high temperatures; at lower temperatures, it's increasingly safe to eat, as are other Pseudomonas species. If the pathogenic threat is temporary, the eventual lapsing of inherited avoidance allows future generations to return to feasting on nutritious Pseudomonas.

"'Transgenerational learned pathogenic avoidance is mediated by TGF-beta and the Piwi/PRG-1 Argonaute pathway" by Rebecca S. Moore, Rachel Kaletsky, and Coleen T. Murphy appears in the June 13 issue of Cell."

Comment: a glimpse into the complex genomic processes that cause epigenetic modifications. So complex that design must have been used

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