A new Northwestern University and University of Texas-Southwestern study has found that bacterial cells can “remember” brief, temporary changes to their bodies and immediate surroundings.
And, while these changes are not encoded in the cell’s genetics, it still passes memories of them to its offspring for generations. That this discovery challenges long-standing assumptions about how even the simplest organisms pass on and receive physical traits is only part of the story; it could also be harnessed for new medical uses. For instance, scientists could bypass antibiotic resistance by subtly altering a pathogenic bacterium such that its progeny would remain more vulnerable to treatment for many generations.
Their findings were published in the journal Science Advances.
A central assumption in bacterial biology is that heritable physical characteristics are determined primarily by DNA,
But, from the perspective of complex systems, we know that information also can be stored at the level of the network of regulatory relationships among genes. We wanted to explore whether there are characteristics transmitted from parents to offspring that are not encoded in DNA, but rather in the regulatory network itself. We found that temporary changes to gene regulation imprint lasting changes within the network that are passed on to the offspring. In other words, the echoes of changes affecting their parents persist in the regulatory network while the DNA remains unchanged.
Adilson Motter
Since molecular underpinnings of genetic code were first identified by 1950s researchers, an intrinsic assumption has been that primarily, if not exclusively, traits are propagated through DNA. Since the completion of the Human Genome Project in 2001, researchers have started revisiting this assumption.
Wytock also refers to the better-known example of non-genetic heritability through the Dutch famine during World War II. Recent research showed that the children of men who, while in utero faced the famine were more likely to gain weight as adults. Isolating the ultimate causes of this type of non-genetic inheritance in humans has proved difficult.
In the case of complex organisms, the challenge lies in disentangling confounding factors such as survivor bias,
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.
Adilson Motter
It is like the communication network that genes have among them to affect one another. The research team apparently believed this network might itself be sufficient reason for traits to be passed down to offspring. To test their idea, Motter and his group turned to Escherichia coli, better known simply as E. coli, a workhorse bacterium that has been under scientific scrutiny for decades.
In the case of E. coli, the entire organism is a single cell,
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.
Thomas Wytock
They modelled the small regulatory network in E. coli to act out transient shutdowns and restarting of single genes. Their results showed such transient disruptions may give long-lasting changes which would be inheritable into many generations. Those predictions are now being tested by the researchers with laboratory experiments using CRISPR engineered to switch off genes temporarily without making permanent edits.
But if the changes are encoded in the regulatory apparatus rather than the DNA sequence, the researchers asked, how might a cell pass those changes on to subsequent generations. They propose that the reversible perturbation triggers a permanent cascade in the regulatory machinery. When one gene is silenced, it sends a signal that affects the next gene downstream in the network. As soon as the prime gene has been reactivated, the cascade will start because these genes are able to build self-sustaining circuits which, after activation, become largely refractory to external influences.
It’s a network phenomenon,
Genes interact with each other. If you perturb one gene, it affects others.
We also could have changed the cell’s environment,
It could be the temperature, the availability of nutrients or the pH.
Adilson Motter
According to the study, additional creatures could possess the components needed to demonstrate non-genetic heredity.
Also, Read| Alzheimer’s disease is caused by a cellular population in the brain
In biology, it’s dangerous to assume anything is universal,
But, intuitively, I do expect the effect to be common because E. coli’s regulatory network is similar or simpler than those found in other organisms.
Adilson Motter
Source: Northwestern Now
Journal Reference: Zhao, Yi, et al. “Irreversibility in Bacterial Regulatory Networks.” Science Advances, 2024, DOI: 10.1126/sciadv.ado3232.
Last Modified:
