Orphan genes are not a distinct biological entity

• Published in: BioEssays Vol. 47; no. 1; pp. e2400146 - n/a
• Main Authors: Pereira, Andres Barboza, Marano, Matthew, Bathala, Ramya, Zaragoza, Rigoberto Ayala, Neira, Andres, Samano, Alex, Owoyemi, Adekola, Casola, Claudio
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2025; John Wiley and Sons Inc
• Subjects: Animals; Biological evolution; DNA Transposable Elements - genetics; Domestication; Evolution, Molecular; Evolutionary genetics; gene evolution; Gene sequencing; Gene transfer; Gene Transfer, Horizontal - genetics; Genes; Genome - genetics; Genomes; Homology; horizontal gene transfer; Horizontal transfer; Humans; Innovations; lineage‐specific genes; ORFans; phenotype; Phylogeny; phylostratigraphy; species; species‐specific genes; taxonomically restricted genes; Think Again; transposons; ORFans; species‐specific genes; lineage‐specific genes; gene evolution; phylostratigraphy; taxonomically restricted genes
• ISSN: 0265-9247; 1521-1878; 1521-1878
• DOI: 10.1002/bies.202400146

The genome sequencing revolution has revealed that all species possess a large number of unique genes critical for trait variation, adaptation, and evolutionary innovation. One widely used approach to identify such genes consists of detecting protein‐coding sequences with no homology in other genomes, termed orphan genes. These genes have been extensively studied, under the assumption that they represent valid proxies for species‐specific genes. Here, we critically evaluate taxonomic, phylogenetic, and sequence evolution evidence showing that orphan genes belong to a range of evolutionary ages and thus cannot be assigned to a single lineage. Furthermore, we show that the processes generating orphan genes are substantially more diverse than generally thought and include horizontal gene transfer, transposable element domestication, and overprinting. Thus, orphan genes represent a heterogeneous collection of genes rather than a single biological entity, making them unsuitable as a subject for meaningful investigation of gene evolution and phenotypic innovation. Orphan genes represent genes with no homologs in other species and are widely assumed to represent genuine species‐specific loci. We show that molecular evolution and sequence homology analyses reject this assumption and that orphan genes constitute a patchwork of genes of different evolutionary ages that originate throughout various mechanisms.