A genome defense in motion

Genome defense refers to how living organisms protect their genetic material from virus-like threats—particularly so-called genetic parasites, which can insert themselves into the genome and disrupt essential processes such as cell division and reproduction.

In the new study, researchers investigated a network of protein interactions central to the fruit fly’s genome defense system. By comparing 12 related Drosophila species, they traced how proteins essential for fertility have evolved over approximately 40 million years.

The research was led by Sebastian Riedelbauch as part of his PhD project at MBG, where he played a key role in uncovering the interplay between evolutionary processes and protein interactions.

“What’s fascinating is that some protein interactions remain remarkably stable — preserved despite major changes in the proteins themselves — while others emerge and disappear depending on the species. This study offers a robust insight into how molecular mechanisms and evolutionary dynamics intersect,” says Peter Ebert Andersen, group leader at MBG.

90,000 experiments and global collaboration

The project was made possible through an extensive international effort involving research groups in Denmark, Austria, Germany, and the United States. It began in Peter Andersen’s group at MBG and took a major leap forward during Sebastian Riedelbauch’s research stay in the lab of Ulrich Stelzl at the University of Graz, Austria.

There, he programmed laboratory robots to carry out over 90,000 interaction assays to systematically test which proteins could bind to each other. Selected interactions were later visualized in living cells during a stay in Mandy Jeske’s group at Heidelberg University in Germany.

Finally, evolutionary analyses of the involved genes were carried out in collaboration with Mia T. Levine’s group at the University of Pennsylvania, USA.

Why it matters

The findings reveal that proteins involved in genome defense are locked in a perpetual evolutionary arms race with virus-like genetic elements. To preserve fertility, organisms must continuously innovate—adapting how proteins interact with each other at a surprising pace.

This work provides valuable insight into how reproductive genes evolve over time and how species adjust to reproductive challenges such as climate change or infections by endogenous viruses.

“In the long run, understanding these mechanisms could help us grasp how fertility is maintained—or lost—across species,” says Peter Ebert Andersen. “It’s basic research, but with wide-ranging relevance, from biodiversity to health.”

Access the study published in EMBO Journal

SUPPLEMENTARY INFORMATION

We strive to ensure that all our articles live up to the Danish universities' principles for good research communication. Against this background, the article is supplemented with the following information:

Study type:

Experiment

External funding:

European Molecular Biology Organization (EMBO): EMBO scientific exchange grant (#10132)

Deutsche Forschungsgemeinschaft (DFG): JE-827/1-1

Novo Nordisk Fonden (NNF): NNF18OC0030954

Danmarks Frie Forskningsfond (DFF): 9064-00056B

Austrian Science Fund (FWF): P30162, P34316

EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA): 754513

University of Graz: Field of Excellence BioHealth

Conflict of interest:

None

The scientific article:

Recurrent innovation of protein-protein interactions in the Drosophila piRNA pathway

Sebastian Riedelbauch, Sarah Masser, Sandra Fasching, Sung-Ya Lin, Harpreet Kaur Salgania, Mie Aarup, Anja Ebert, Mandy Jeske, Mia T Levine, Ulrich Stelzl, Peter Andersen.

Contact information:

Associate Professor Peter Ebert Andersen
Department of Molecular Biology and Genetics
Aarhus University
pra@mbg.au.dk