Bacteria related findings establish that temporary stress can cause heritable changes without altering the genetics.
Northwestern University researchers have established that bacterial cells can ‘remember’ brief, temporary changes to their bodies and immediate surroundings. Although these changes are not encoded in the cell’s genetics, the cell still passes memories of them to its offspring — for multiple generations.
Scientists had earlier discovered that bacteria can create something like memories about when to form strategies that can cause dangerous infections in people, such as resistance to antibiotics.
This new discovery challenges long-held assumptions of how the simplest organisms transmit and inherit physical traits. In addition, the findings can be leveraged for new medical applications. For example, researchers could circumvent antibiotic resistance by subtly tweaking a pathogenic bacterium to render its offspring more sensitive to treatment for generations.
Lead researcher, Northwestern’s Adilson Motter, clarifies the research significance as: “A central assumption in bacterial biology is that heritable physical characteristics are determined primarily by DNA.”
However, he adds: “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.”
Furthermore, the academic states: “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.”
Since scientists first identified the molecular underpinnings of genetic code in the 1950s, they have assumed traits are primarily — if not exclusively — transmitted through DNA. However, after the completion of the Human Genome Project in 2001, researchers have revisited this assumption.
The researchers cite 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.
Motter adds: “In the case of complex organisms, the challenge lies in disentangling confounding factors such as survivor bias. But perhaps w e 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.”
The regulatory network is analogous to a communication network that genes use to influence each other.
The research team hypothesized that this network alone could hold the key to transmitting traits to offspring. To explore this hypothesis, Motter and his team turned to Escherichia coli (E. coli), a common bacterium and well-studied model organism.
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.
The research appears in the journal Science Advances, titled “Irreversibility in bacterial regulatory networks.”