A recent study on the functions of human protein-coding genes, published in the prestigious journal Nature, marks a significant advancement in the functional characterisation of the human genome. The research was conducted by an international team of scientists, including Dr Àlex Bayés from the Sant Pau Research Institute (IR Sant Pau), the sole investigator from a Spanish research centre involved in the project.
The study presents the most comprehensive compilation to date of human gene functions, effectively forming what could be termed the human functionome. This invaluable source of information holds profound implications for both basic and biomedical research.
The project integrates data obtained directly from human gene studies with a comparative evolutionary analysis. This methodological approach has enabled researchers to infer nearly 70,000 functions, covering 82% of human genes. Previous studies had identified functions for only 40–60% of protein-coding human genes. Notably, around 60% of these inferred functions stem from the evolutionary approach applied in this study.
Furthermore, the evolutionary study has provided insights into the origins of human gene functions. Paradoxically, the findings suggest that most of these functions are highly ancestral, predating the emergence of multicellular organisms more than 1.6 billion years ago, and have remained largely conserved throughout this period. The last major evolutionary wave of new functions is believed to have occurred with the emergence of placental mammals around 100 million years ago. Since then, few new functions have been added to the human genome’s repertoire.
This work was made possible through the support of PAN-GO (Phylogenetic Annotation of Gene Ontology), an innovative platform that integrates phylogenetic data to enhance the precision of functional gene descriptions. The use of PAN-GO has been instrumental in identifying evolutionary patterns in gene function and in generating a more complete and accurate compendium of gene roles in human biology.
The participation of IR Sant Pau in this study reaffirms the institute’s scientific excellence and its contribution to cutting-edge basic and biomedical research on a global scale. Collaborating in such projects strengthens the role of Spanish science in high-impact international initiatives.
“We have had the tremendous privilege of contributing to a global scientific initiative aimed at systematising the knowledge generated by the scientific community on human gene functions, creating indispensable computational analysis tools for biomedical research,” said Dr Bayés.
Feuermann M, Mi H, Gaudet P, Muruganujan A, Lewis SE, Ebert D, et al. A compendium of human gene functions derived from evolutionary modelling. Nature 2025:1–9. https://doi.org/10.1038/s41586-025-08592-0
