"Wytock cites the World War II Dutch famine as a famous example pointing
to the possibility of heritable, non-genetic traits in humans. A recent
study showed that the children of men, who were exposed to the famine in
utero, exhibited an increased tendency to become overweight as adults.
But isolating the ultimate causes for this type of non-genetic
inheritance in humans has proved challenging.

"In the case of complex organisms, the challenge lies in disentangling confounding factors such as survivor bias," Motter said. "But perhaps we
can isolate the causes for the simplest single-cell organisms, since we
can control their environment and interrogate their genetics. If we
observe something in this case, we can attribute the origin of
non-genetic inheritance to a limited number of possibilities -- in
particular, changes in gene regulation."
..

"In the case of E. coli, the entire organism is a single cell," Wytock
said. "It has many fewer genes than a human cell, some 4,000 genes as
opposed to 20,000. It also lacks the intracellular structures known to
underlie the persistence of DNA organization in yeast and the
multiplicity of cell types in higher organisms.Because E. coli is a well-studied model organism, we know the organization of the gene
regulatory network in some detail."

Reversible stress, irreversible change

The research team used a mathematical model of the regulatory network to simulate the temporary deactivation (and subsequent reactivation) of
individual genes in E. coli. They discovered these transient
perturbations can generate lasting changes, which are projected to be
inherited for multiple generations. The team currently is working to
validate their simulations in laboratory experiments using a variation
of CRISPR that deactivates genes temporarily rather than permanently.

But if the changes are encoded in the regulatory network rather than the
DNA, the research team questioned how a cell can transmit them across generations. They propose that the reversible perturbation sparks an irreversible chain reaction within the regulatory network. As one gene deactivates, it affects the gene next to it in the network. By the time
the first gene is reactivated, the cascade is already in full swing
because the genes can form self-sustaining circuits that become
impervious to outside influences once activated.

"It's a network phenomenon," said Motter, who is an expert in the
dynamic behaviors of complex systems. "Genes interact with each other.
If you perturb one gene, it affects others."

https://www.sciencedaily.com/releases/2024/08/240828154929.htm

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