Comparative evolutionary genomics has revealed that novel protein coding genes can emerge randomly from non-coding DNA. While most of the myriad of transcripts which continuously emerge vanish rapidly, some attain regulatory regions, become translated and survive. More surprisingly, sequence properties of de novo proteins are almost indistinguishable from randomly obtained sequences, yet de novo proteins may gain functions and integrate into eukaryotic cellular networks quite easily. We here discuss current knowledge on de novo proteins, their structures, functions and evolution. Since the existence of de novo proteins seems at odds with decade-long attempts to construct proteins with novel structures and functions from scratch, we suggest that a better understanding of de novo protein evolution may fuel new strategies for protein design.

Department of Cell Biology Faculty of Science Charles University Biocev Prague Czech Republic; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Gilead Sciences and IOCB Research Center Flemingovo nám 2 166 10 Prague Czech Republic

Institute for Evolution and Biodiversity University of Muenster Huefferstraße 1 48149 Muenster Germany

Institute for Evolution and Biodiversity University of Muenster Huefferstraße 1 48149 Muenster Germany; Department of Protein Evolution MPI for developmental Biology Tuebingen Germany

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