Most lethal mutations in wild fruit flies are driven by newly transferred jumping genes, not small DNA errors, according to a new study from Duke University.
The findings, published in PLOS Biology , challenge decades of assumptions in evolutionary genetics and may have implications for population health and conservation.
“Almost every individual of any species studied has at least one lethal mutation,” said lead author Sarah Marion, who began this work as a biology graduate student at Duke and is now a postdoctoral researcher at Reed College. “I thought, how is that possible? Wouldn’t natural selection remove that?”
In theory, lethal mutations should disappear quickly under natural selection. But in reality, their frequency reflects a balance between how often new mutations arise and how efficiently selection removes them.
To better understand this balance and what drives mutations, the team trapped wild fruit flies using buckets baited with rum, bananas and yeast. From these collections, they identified roughly 300 fly lineages that carried lethal mutations on one chromosome.
Over the course of 5 years and 21,000 pairings of flies, the research team were able to chart the population-level dynamics of mutations. They discovered that most lethal mutations were caused not by small DNA changes, as expected, but by two transposable elements that had recently jumped from another fruit fly species.
Transposable elements – also called transposons or jumping genes – are pieces of DNA that can move around within a genome. Some make a copy of themselves and insert that copy somewhere new. Others cut themselves out and move to a different spot. When they land inside an important gene, they can interrupt how that gene works and sometimes break it entirely.
“Going in, I kind of naively thought we would find single nucleotide changes or small deletions,” Marion said. “The fact that these transposable elements were the main lethal culprits really surprised me.”
First discovered in corn and once dismissed as “junk DNA,” transposable elements actually make up 20% to 80% of many genomes. The research reveals that these jumping genes can act like an invasive force: When a new transposable element enters a species, it triggers a high-speed mutation spike that temporarily outpaces natural selection.
“We are just now, as a scientific community, starting to understand the importance and impact of transposons,” said Marion.
The researchers found that over time, host genomes evolve immune responses to silence these invaders. This creates a cycle where lethal mutation rates fluctuate, spiking during an invasion and declining as genomic defenses take hold.
“What amazes me most is that we’re seeing the same proportion of lethal mutations that scientists reported more than 50 years ago, but the genetic culprits are entirely different,” said professor of biology Mohamed Noor, senior author on the study. “In our case, they’re all recent invaders, revealing a hidden and fast-moving layer of evolution.”
This discovery has immediate stakes for conservation biology. In small or endangered populations, these genomic storms can trigger rapid population declines through inbreeding and genetic drift. Identifying these mechanisms could help monitor and improve the long-term genetic health of at-risk species.
The findings reshape the understanding of how harmful genetic variants arise and persist in populations. For decades, evolutionary theory has emphasized small DNA changes as the primary source of genetic variation, and thus, by extension, lethal mutations. This research suggests that transposons jumping in and breaking existing genes may play a much greater role than previously recognized. Transposable elements are also known to contribute to some human diseases, and as genome sequencing technologies improve, researchers are finding that large insertions may be more common than once thought.
Marion is continuing to investigate the genetics of the fruit flies bred for this research. She is also expanding the work to examine mutation rates across related species, asking how often different classes of transposable elements move within the genome and why these rates may differ between species. Understanding these differences could reveal molecular or evolutionary mechanisms shaping how often and at what locations transposable elements mobilize in the genome.
This research was supported by the National Science Foundation. Federal funding was essential to carrying out the large-scale experimental fly crosses, long-term population maintenance, and genome sequencing required for the study.
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Funding: This work was supported by a National Science Foundation grant (DEB 2019789).
REFERENCE: Transposable elements contribute substantially to naturally occurring genetic lethality in Drosophila melanogaster . Sarah B. Marion, Katrina Focht, Iman Hamid, Edwin S Iversen, Hannah John, Brenda Manzano-Winkler, Amber Navarra, Saniya Pangare, Mehrnaz Zarei, and Mohamed A. F. Noor. PLOS Biology, 2026. DOI: 10.1371/journal.pbio.3003467 .
PLOS Biology
Experimental study
Animals
Transposable elements contribute substantially to naturally occurring genetic lethality in Drosophila melanogaster
10-Mar-2026