Bacteria pass down ‘memories’ to future generations

Bacteria have the remarkable ability to “remember” brief, temporary changes to their bodies and surroundings, and these memories are heritable, according to a recent study led by Northwestern University.

Interestingly, while these changes are not encoded in the bacterial cell’s genetic material, the cell can still pass the memory of these changes to its offspring for multiple generations.

Manipulating the memories of bacteria

This finding challenges long-held assumptions about how even the simplest organisms transmit and inherit physical traits, and it could have significant implications for medical applications. 

For example, researchers might be able to combat antibiotic resistance by subtly altering a pathogenic bacterium in a way that makes its offspring more susceptible to treatment over several generations.

“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 can also be stored at the level of the network of regulatory relationships among genes,” explained senior author Adilson Motter, a scientist at Northwestern.

Bacteria memories persist in the regulatory network 

According to Motter, the team wanted to explore whether bacteria memories could be transmitted from parents to offspring not through DNA, but through the regulatory network itself.

“We found that temporary changes to gene regulation can imprint lasting changes within the network, which are then passed on to the offspring,” said Motter. 

“In other words, the echoes of changes affecting their parents persist in the regulatory network while the DNA remains unchanged.”

Motter, who is the Charles E. and Emma H. Morrison Professor of Physics at Northwestern’s Weinberg College of Arts and Sciences and director of the Center for Network Dynamics, co-authored the study with postdoctoral fellow Thomas Wytock and graduate student Yi Zhao from his lab. 

The study was conducted in collaboration with Kimberly Reynolds, a systems biologist at the University of Texas-Southwestern Medical Center.

Non-genetic inheritance in humans 

Since the molecular basis of the genetic code was identified in the 1950s, scientists have generally assumed that traits are transmitted primarily, if not exclusively, through DNA. 

However, since the completion of the Human Genome Project in 2001, researchers have begun to reconsider this assumption.

Wytock points to the World War II Dutch famine as a well-known example of potential non-genetic inheritance in humans. 

A recent study showed that children of men who were exposed to the famine in utero were more likely to become overweight as adults. However, isolating the exact causes of this type of non-genetic inheritance in humans has proven difficult.

“In complex organisms, it’s challenging to disentangle confounding factors like survivor bias. But in the simplest single-cell organisms, where we can control the environment and examine their genetics, we can isolate the causes more effectively,” explained Motter.  

“If we observe something in this case, we can attribute the origin of non-genetic inheritance to a limited number of possibilities, particularly changes in gene regulation.”

The gene regulatory network 

The gene regulatory network is similar to a communication network that genes use to influence one another. The research team hypothesized that this network alone might be key to transmitting traits to offspring. 

To test this hypothesis, Motter and his team studied Escherichia coli (E. coli), a common bacterium that serves as a well-established model organism.

“In E. coli, the entire organism is a single cell,” Wytock explained. “It has many fewer genes than a human cell, about 4,000 compared to 20,000. It also lacks the intracellular structures that contribute to DNA organization in yeast and the variety of cell types in higher organisms. Because E. coli is so well-studied, we know a great deal about the organization of its gene regulatory network.”

Heritable changes across generations 

Using a mathematical model of the regulatory network, the research team simulated the temporary deactivation and reactivation of individual genes in E. coli. They found that these brief disruptions could cause lasting changes, which are likely to be inherited for multiple generations. 

The team is now working to validate these simulations through laboratory experiments using a variation of CRISPR that temporarily deactivates genes rather than permanently altering them.

Cascading effects of bacterial cell changes

The researchers questioned how these changes, encoded in the regulatory network rather than the DNA, could be transmitted across generations. They propose that a reversible perturbation might trigger an irreversible chain reaction within the regulatory network. 

When one gene is deactivated, it impacts neighboring genes in the network. By the time the first gene is reactivated, a self-sustaining cascade has already begun, creating circuits that become resistant to outside influences once activated.

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

Broader implications of the study

Although the current experiments focus on deactivating genes, Motter noted that other types of perturbations could have similar effects. 

“We could also change the cell’s environment,” he said. “For example, it could be temperature, nutrient availability, or pH levels.”

The study suggests that other organisms could also exhibit non-genetic heritability. 

“In biology, it’s dangerous to assume anything is universal,” Motter cautioned. “But, intuitively, I expect this effect to be common because E. coli’s regulatory network is similar to or simpler than those found in other organisms.”

The study is published in the journal Science Advances.

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