A research team led by the University of Texas at Austin has identified previously unknown genes linked to three rare disorders by reconstructing an ancient map of protein interactions shared across complex life. Published in Cell Genomics, the study presents the most detailed reconstruction yet of the protein interactome of the Last Eukaryotic Common Ancestor, or LECA, a single-celled organism that lived about 1.5-1.8 billion years ago and gave rise to all modern eukaryotes, including animals, plants, fungi and humans.

Proteins rarely act alone. They assemble into molecular machines that generate energy, transport materials, build cellular structures and remove waste. Because many of these systems are essential, their components have been conserved over vast evolutionary timescales. Mutations in the genes encoding them can therefore contribute to serious human diseases. To reconstruct LECA’s molecular machinery, researchers compared genes and proteins from 156 eukaryotic organisms. They then analyzed more than 25,000 biochemical experiments involving 31 species, using mass spectrometry and powerful supercomputers at the Texas Advanced Computing Center to determine which ancient proteins interacted with one another.

The resulting network became a tool for disease discovery. By mapping known disease-associated proteins onto the interactome, the team identified nearby proteins that might also contribute to the same conditions – an approach known as “guilt by association”. Using frog and mouse models, researchers confirmed new gene associations with three rare disorders: osteopetrosis, end-stage kidney disease and short-rib thoracic dysplasia. The map also revealed hundreds of additional ancient genes that may be involved in human disease and could guide future studies.

The research highlights how deeply human biology is connected to the evolutionary history of other organisms. About half of human genes, the team found, can be traced back to versions already present in LECA. Future work will use animal models to test additional disease-gene links predicted by the ancient protein network. Understanding the evolving of evolution might help in our studying of extraterrestrial life.

For more details, read the full article by University of Texas.