ArticleGenome biology and evolution2020
Stochastic Gain and Loss of Novel Transcribed Open Reading Frames in the Human Lineage.
Article in Genome biology and evolution, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- DetectNAR genomics and bioinformatics · 2026Article
- Review
- Deeply conserved and expressed small ORFs in the model beetle Tribolium castaneum.BMC biology · 2026Article
- Emergence and evolution of protein-coding de novo genes.Nature reviews. Genetics · 2026Review
- Orthologs of an essential orphan gene vary in their capacities for function and subcellular localization in Drosophila melanogaster.Molecular biology and evolution · 2026Article
- Emergence and Tandem Repeat-Mediated Elongation of a Translated De Novo Open Reading Frame in Human Oncogenic RNA Gene VPS9D1-AS1 (MYU).Genome biology and evolution · 2026Article
- De Novo Gene Emergence: Summary, Classification, and Challenges of Current Methods.Genome biology and evolution · 2025Review
- Emergence of antiphage functions from random sequence libraries reveals mechanisms of gene birth.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DeNoFo: a file format and toolkit for standardized, comparable de novo gene annotation.Bioinformatics (Oxford, England) · 2025Article
- Comprehensive profiling of ribo-seq detected small sequences in yeast reveals robust conservation patterns and their potential mechanisms of origin.BMC genomics · 2025Article
- Modeling Length Changes in De Novo Open Reading Frames during Neutral Evolution.Genome biology and evolution · 2024Article
- The Rapid Evolution of De Novo Proteins in Structure and Complex.Genome biology and evolution · 2024Article
- High-throughput Selection of Human de novo-emerged sORFs with High Folding Potential.Genome biology and evolution · 2024Article
- Towards understanding paleoclimate impacts on primate de novo genes.G3 (Bethesda, Md.) · 2023Article
- Thousands of Pristionchus pacificus orphan genes were integrated into developmental networks that respond to diverse environmental microbiota.PLoS genetics · 2023Article
- Evolution and implications of de novo genes in humans.Nature ecology & evolution · 2023Review
- Population genomics reveals mechanisms and dynamics of de novo expressed open reading frame emergence inGenome research · 2023Article
- Experimental characterization of de novo proteins and their unevolved random-sequence counterparts.Nature ecology & evolution · 2023Article
- Assessing structure and disorder prediction tools forF1000Research · 2023Article
- De novo birth of functional microproteins in the human lineage.Cell reports · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In addition to known genes, much of the human genome is transcribed into RNA. Chance formation of novel open reading frames (ORFs) can lead to the translation of myriad new proteins. Some of these ORFs may yield advantageous adaptive de novo proteins. However, widespread translation of noncoding DNA can also produce hazardous protein molecules, which can misfold and/or form toxic aggregates. The dynamics of how de novo proteins emerge from potentially toxic raw materials and what influences their long-term survival are unknown. Here, using transcriptomic data from human and five other primates, we generate a set of transcribed human ORFs at six conservation levels to investigate which properties influence the early emergence and long-term retention of these expressed ORFs. As these taxa diverged from each other relatively recently, we present a fine scale view of the evolution of novel sequences over recent evolutionary time. We find that novel human-restricted ORFs are preferentially located on GC-rich gene-dense chromosomes, suggesting their retention is linked to pre-existing genes. Sequence properties such as intrinsic structural disorder and aggregation propensity-which have been proposed to play a role in survival of de novo genes-remain unchanged over time. Even very young sequences code for proteins with low aggregation propensities, suggesting that genomic regions with many novel transcribed ORFs are concomitantly less likely to produce ORFs which code for harmful toxic proteins. Our data indicate that the survival of these novel ORFs is largely stochastic rather than shaped by selection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.