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• W3105446189 abstract "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." @default.
• W3105446189 created "2020-11-23" @default.
• W3105446189 creator A5003109713 @default.
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• W3105446189 date "2020-09-16" @default.
• W3105446189 modified "2023-10-12" @default.
• W3105446189 title "Stochastic Gain and Loss of Novel Transcribed Open Reading Frames in the Human Lineage" @default.
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• W3105446189 doi "https://doi.org/10.1093/gbe/evaa194" @default.
• W3105446189 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7674706" @default.
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