Reconstructed 1.5‑billion‑year‑old protein network reveals hundreds of hidden disease‑linked genes

Key Points:

• A University of Texas at Austin-led team has reconstructed the most detailed protein interactome map of the Last Eukaryotic Common Ancestor (LECA), an ancient single-celled organism from which all complex life descended, revealing genetic links to human diseases.
• By analyzing protein networks conserved for over a billion years, the researchers identified hundreds of genes not previously associated with diseases and confirmed connections between three genes and rare disorders using animal models and patient data.
• The study highlights how ancient molecular machines formed by proteins are critical to life and how mutations in genes encoding these proteins can cause diseases, with some genes showing conserved functions across diverse species.
• The team used biochemical experiments on 31 eukaryotic species and supercomputer analysis to reconstruct LECA's protein interactome, enabling them to predict gene-disease associations by mapping known disease proteins and their interacting partners.
• This research offers new insights into the evolutionary origins of human diseases and may guide future studies to experimentally validate additional disease-related genes, potentially leading to novel therapeutic targets.