A genome contains all of the DNA of every living organism, but its contents don't stop there - most of these structures also contain snippets of DNA that can copy and paste themselves to "infect" a genome, expanding its size. Precisely why that happens remains a mystery.
Researchers have created a new computational tool that works from an inferred ancestral point and evolves forward to the modern-day genome to trace the insertion and deletion dynamics of these "jumping genes," known as transposable elements.
Scientists at The Ohio State University who study how transposable elements, also called transposons or TEs, may have altered gene functions over time were looking for the best way to trace that evolutionary history, so they created the simulator they needed to do the work.
"In the timescale of millions or tens of millions of years, transposon activity is really dense. There are many, many transposon insertions and deletions to the genome and from the genome," said senior study author Shujun Ou, assistant professor of molecular genetics at Ohio State.
"We want to use the footprint of that activity to study what may have happened in the past because we'll never know for sure, but we can infer what may be the case in terms of transposon activity."
Their initial findings from a case study on fungal genomes hinted at how bursts of TE insertions were followed by deletions, suggesting the fungus fought back to suppress further insertions.
Ou and colleagues describe the PrinTE simulator today (Nov. 2, 2026) in Nature Communications.
The corn genome is perhaps the best-known example of the transposon effect on genome expansion: Up to 85% of its genome consists of jumping genes, said first author Christopher Benson, a postdoctoral scholar in Ou's lab.
"These are big components of a genome that maybe don't necessarily have a noticeable impact, but they exist. They're functioning in the background in these ways that we're still trying to understand," Benson said.
"But one thing that they do is impact genome size evolution heavily because they often insert as a copy-and-paste. You have the original copy and the duplicated copy. So if you do this tons of times, you get a really enormous genome."
This phenomenon is known as the genome size paradox: Plants with major differences in genome size function in the same way.
"Is there any value of having a genome that's bigger or smaller? It's paradoxical because if genome size is important, the larger genome plants must have more actual function or a more complicated structure," Ou said. "But in observation, they don't."
Ou and Benson designed PrinTE as an enhancement of a previous tool called TEGenomeSimulator, which provides a snapshot of transposon infection of a genome at a single point in time. Ou's lab collaborated with the New Zealand-based creators of TEGenomeSimulator, who are co-authors on the paper.
The case study focused on the fungal subdivision that includes the species myrtle rust, whose genome has expanded to 1 billion base pairs - enormous by fungal standards - because of transposon insertions. Starting with its present-day genome, the team reconstructed a genome from a theoretical common ancestor, hypothesized the variety of ways the ancestral genome could evolve into the current genome, and ran simulations to test those predictions.
"We'll play the simulator forward to try to make the present-day fungus. Sometimes it takes thousands of simulations to find the one that best fits, but this allows us to test those hypotheses that we've typically been looking at but not addressing in full depth," Benson said.
Because the simulation is covering millions of generations of evolution, PrinTE built a safeguard to detect and terminate trajectories headed in the wrong direction to maximize efficiency.
"Beginning a simulation is like walking in the dark," Ou said, "because we only see the outcome, but we don't know what happened in the past. There can even be times when we're walking in the wrong direction. So we use machine learning to guide us to walk in the right direction, or closer to the right direction."
The simulations in myrtle rust showed that the TE insertion rate was 4 to 5 times higher than the deletion rate, causing the excessively large genome, and these bursts were then followed by a drop in insertions, which is a sign of tightened control of TE activity.
"The finding suggests inserted TEs can eventually be purged by the host to suppress their activity - sort of how the immune system takes some time to catch up with an infection," Benson said.
"One main conclusion in this paper is that the most effective way to control the genome size is to not have any infection in the first place," Ou said.
He said this work provides a gold standard for understanding transposon evolutionary history and may one day open the door for genomic rescue to slow TE activity or delete TEs in species struggling to survive.
The publicly available tool has already been used by scientists studying other systems.
The research was supported by Ohio State's STEM Education Faculty Startup Award, a U.S. Department of Agriculture postdoctoral fellowship, the U.S. National Science Foundation and the Bioeconomic Science Institute in New Zealand.
