Many proteins for which there is no experimental evidence have been predicted from the genomes of various species. Researchers have now doubled the number of experimentally detected proteins. Matthias Mann of the Max Planck Institute of Biochemistry and the University of Copenhagen and coworkers now report their proteomic analysis of 100 species, the largest cross-species comparative proteomics study to date (Nature 2020, DOI: 10.1038/s41586-020-2402-x). They analyzed the proteomes of 19 single-celled organisms known as archaea, 49 bacteria, and 32 eukaryotes, including many well-studied model organisms. In the whole set, they identified more than 2 million peptides and 349,164 proteins. About 93% of these peptides and proteins are ones found in TrEMBL, the portion of the UniProt protein database that includes sequences predicted from genomes but not experimentally detected. The researchers found previously undetected proteins even in extensively studied model organisms. Overall, more than 38% of the identified proteins have unknown biological functions. Among the 100 most abundant proteins for each species, nearly 23% have unknown functions. “These proteins may indicate essential but unique features in the evolutionary development of these organisms that may be of biological or biotechnological interest,” the researchers write.