Bacterial cells have the ability to ‘remember’ short-term changes in their environment and their own structure, according to a recent study. Interestingly, these temporary alterations are not recorded in the DNA, yet the memories are still passed down to their descendants across several generations.
Recent research from Northwestern University and the University of Texas-Southwestern reveals that bacterial cells can “remember” fleeting changes in their bodies and their surroundings.
Even though these adaptations are not coded into the cell’s genetic material, the cells convey these memories to their offspring over multiple generations.
This finding not only questions traditional beliefs about how even the simplest living organisms pass on physical traits, but it also holds potential for innovative medical advancements. For example, scientists could strategically alter a harmful bacterium to make its progeny more susceptible to antibiotics for generations.
The study is set to appear in the journal Science Advances on Wednesday (Aug. 28).
“A key belief in bacterial biology is that heritable physical traits are mainly determined by DNA,” stated Adilson Motter from Northwestern, who is the lead author of the study. “However, when viewed through the lens of complex systems, we understand that information can also be preserved through the interconnected relationships among genes. We wanted to investigate whether traits could be passed from parent to offspring without being encoded in DNA, but instead through the regulatory network itself. Our findings suggest that temporary shifts in gene regulation can leave lasting imprints in the network that are inherited by offspring. In other words, the impacts of changes affecting parents linger in the regulatory network while the genetic material remains unchanged.”
Motter holds the position of Charles E. and Emma H. Morrison Professor of Physics at Northwestern’s Weinberg College of Arts and Sciences and is the director of the Center for Network Dynamics. The lead authors of the study include postdoctoral fellow Thomas Wytock and graduate student Yi Zhao, both from Motter’s lab, alongside Kimberly Reynolds from the University of Texas Southwestern Medical Center.
Insights from a model organism
Since the discovery of the genetic code’s molecular basis in the 1950s, it has been widely accepted that traits are primarily passed down through DNA. However, following the finish of the Human Genome Project in 2001, researchers have reevaluated this notion.
Wytock references the Dutch famine during World War II as a significant case pointing to the potential for inheritable, non-genetic traits in humans. A recent study indicated that the children of men who experienced famine while in utero showed a higher likelihood of becoming overweight in adulthood. Nevertheless, identifying the ultimate causes of such non-genetic inheritance in humans has proven to be difficult.
“For complex organisms, uncovering the true causes is complicated by factors like survivor bias,” Motter explained. “But with simpler single-celled organisms, we can manipulate their environment and conduct genetic investigations more easily. If we observe non-genetic inheritance here, we can link it to a limited set of causes, particularly changes in gene regulation.”
The regulatory network serves as a communication pathway allowing genes to affect one another. The research team hypothesized that this network could be crucial for passing traits to the next generation. To explore this idea, they investigated Escherichia coli (E. coli), a well-researched bacterium and standard model organism.
“E. coli is a single-celled organism,” Wytock noted. “It contains significantly fewer genes than a human cell—about 4,000 genes compared to 20,000 in humans. It also lacks the intracellular structures that help maintain DNA organization in yeast and more complex organisms. Since E. coli is a thoroughly studied model organism, we understand its gene regulatory network quite well.”
Temporary stress leads to lasting change
The research team employed a mathematical model of the regulatory network to simulate the temporary shutdown (and subsequent restart) of specific genes in E. coli. They discovered that these short-term changes could produce enduring alterations projected to be inherited across various generations. They are currently validating their simulations through laboratory experiments using a modified version of CRISPR that temporarily inactivates genes instead of permanently altering them.
However, the team questioned how a cell could pass these regulatory network changes onto its descendants if those changes aren’t part of the DNA. They suggest that these reversible changes ignite an irreversible chain reaction within the regulatory network. As one gene is turned off, it subsequently influences its neighboring gene. Once the first gene is turned back on, the cascading effects are already in progress, as the genes can form self-sustaining circuits that are resistant to outside changes once activated.
“It’s a network phenomenon,” Motter remarked, emphasizing his expertise in the dynamics of complex systems. “Genes interact with each other. If one gene is disrupted, it affects others.”
Though his team is testing the hypothesis by inactivating genes, Motter points out that different types of disruptions could yield similar results. “We could also have altered the cell’s environment,” he said, highlighting factors such as temperature, nutrient availability, or pH levels.
The study implies that other organisms might also exhibit elements of non-genetic inheritance. “In biology, it’s risky to assume universality,” Motter commented. “But intuitively, I believe this effect to be widespread since E. coli’s regulatory network is either similar to or simpler than those found in other organisms.”
The research titled “Irreversibility in bacterial regulatory networks” was funded by the National Science Foundation (award number MCB-2206974).
