Evolution and implications of de novo genes in humans

Luuk A Broeils, Jorge Ruiz-Orera, Berend Snel, Norbert Hubner, Sebastiaan van Heesch

Research output: Contribution to journalArticlepeer-review


Genes and translated open reading frames (ORFs) that emerged de novo from previously non-coding sequences provide species with opportunities for adaptation. When aberrantly activated, some human-specific de novo genes and ORFs have disease-promoting properties-for instance, driving tumour growth. Thousands of putative de novo coding sequences have been described in humans, but we still do not know what fraction of those ORFs has readily acquired a function. Here, we discuss the challenges and controversies surrounding the detection, mechanisms of origin, annotation, validation and characterization of de novo genes and ORFs. Through manual curation of literature and databases, we provide a thorough table with most de novo genes reported for humans to date. We re-evaluate each locus by tracing the enabling mutations and list proposed disease associations, protein characteristics and supporting evidence for translation and protein detection. This work will support future explorations of de novo genes and ORFs in humans.

Original languageEnglish
Pages (from-to)804-815
Number of pages12
JournalNature ecology & evolution
Issue number6
Early online date16 Mar 2023
Publication statusPublished - Jun 2023


  • Exons
  • Humans
  • Open Reading Frames


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