De novo birth of functional microproteins in the human lineage.

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Vakirlis, Nikolaos; Vance, Zoe; Duggan, Kate M; McLysaght, Aoife
Year of Publication: 2022
Journal: Cell Rep
Volume: 41
Issue: 12
Pagination: 111808
Date Published: 2022 Dec 20
Publication Language: eng
ISSN: 2211-1247
Keywords: Animals, Evolution, Molecular, Genome, Hominidae, Humans, Open Reading Frames, Pan troglodytes

Small open reading frames (sORFs) can encode functional "microproteins" that perform crucial biological tasks. However, their size makes them less amenable to genomic analysis, and their origins and conservation are poorly understood. Given their short length, it is plausible that some of these functional microproteins have recently originated entirely de novo from noncoding sequences. Here we sought to identify such cases in the human lineage by reconstructing the evolutionary origins of human microproteins previously found to have measurable, statistically significant fitness effects. By tracing the formation of each ORF and its transcriptional activation, we show that novel microproteins with significant phenotypic effects have emerged de novo throughout animal evolution, including two after the human-chimpanzee split. Notably, traditional methods for assessing coding potential would miss most of these cases. This evidence demonstrates that the functional potential intrinsic to sORFs can be relatively rapidly and frequently realized through de novo gene emergence.

DOI: 10.1016/j.celrep.2022.111808
Alternate Journal: Cell Rep