New study sheds light on how bacteria evolve and adapt

An interdisciplinary team of researchers, including some from Arizona State University, is taking a closer look at a hidden driver of bacterial evolution — tiny DNA rings called plasmids — to understand how they help bacteria adapt, survive and spread traits like antibiotic resistance.

The team’s findings are detailed in a newly published article in the Proceedings of the National Academy of Sciences, titled "Plasmid mutation rates scale with copy number."

Bacteria can adapt very quickly to new environments, including learning how to survive antibiotics. One of the reasons they can do this is through plasmids, which are small circular pieces of genetic material that live inside bacteria but are separate from their main DNA.

Plasmids are especially important because they often carry genes that give bacteria antibiotic resistance. A key open question is how fast plasmids evolve. In particular, bacteria usually carry many copies of the same plasmid, and scientists have long debated whether having more copies makes plasmids evolve faster or slower — a question this interdisciplinary project set out to answer using a combination of biological experiments and mathematical modeling.

“This project highlights the importance of interdisciplinary research. Solving real-world problems like antibiotic resistance requires close collaboration between experimentalists, computational scientists, and mathematicians,“ said Adrian Gonzalez Casanova, associate professor in ASU’s School of Mathematics and Statistical Sciences and the Center for Mechanisms of Evolution in the Biodesign Institute. Gonzales was responsible for the mathematical part of the project.

“As a mathematician, I see this as a powerful example of how abstract theory can contribute meaningfully to urgent biological and medical questions when researchers from different fields work together.”

Read the below Q&A to learn more about Gonzalez's work and why this research matters.

Note: This interview has been edited lightly for length and/or brevity.

Question: What was the conclusion of this research?

Answer: We found that plasmids with more copies do accumulate more successful mutations, but not too fast. Instead of increasing rapidly or decreasing, the number of surviving mutations grows logarithmically as the number of plasmid copies increases.

In simple terms, this means that having more plasmid copies does increase the evolutionary rate, but with diminishing returns. Even so, because this growth continues as copy number increases, plasmids with many copies still act as important drivers of bacterial evolution.

Q: How did you get involved in this research project?

A: This project combined experiments, computer simulations and mathematics. The experimental team designed a clever system where the same bacteria could be studied with different plasmid copy numbers, allowing a clean comparison.

Once the experiments were designed by a team lead — by Jeronimo Rodriguez-Beltran and championed by Paula Ramiro Martinez, both from the Microbiology Department (at the) Hospital Universitario Ramón y Cajal (and the) Instituto Ramón y Cajal de Investigación Sanitaria (in) Madrid, Spain — the team needed theoretical predictions to understand what patterns to expect. I became involved through my long-standing collaboration with biologist Rafael Peña-Miller — from the Centro de Ciencias Genómicas (of the) Universidad Nacional Autónoma de México — who invited me to help interpret the problem using population genetics theory.

Q: What was your role?

A: I was responsible for the mathematical part of the project. Using classical population genetics models, I translated the biological question into a well-studied mathematical framework that describes how genetic lineages evolve over time.

This allowed us to make precise predictions about how mutations should accumulate depending on plasmid copy number. These predictions were later confirmed by both experiments and simulations.

Q: How was your contribution important?

A: The mathematical analysis revealed that the relationship between plasmid copy number and evolution follows a logarithmic law. This kind of slow-growing pattern is extremely difficult to guess just by looking at experimental data.

Providing a mathematical explanation helped confirm that the observed results were not accidental, and it showed that classical genetic models, originally developed for much larger organisms, still apply to modern problems like bacterial evolution.

Q: What applications to everyday life might this research have?

A: Antibiotic resistance is one of the most urgent medical challenges we face. Bacteria often evolve resistance faster than we can develop new antibiotics, and plasmids play a central role in this process.

By better understanding how plasmids evolve, we gain insight into why resistance spreads so quickly and what factors accelerate or slow it down. This knowledge could eventually help guide strategies to manage antibiotic use and slow the spread of resistance.