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Readthrough Errors Purge Deleterious Cryptic Sequences, Facilitating the Birth of Coding Sequences.

Luke J Kosinski1, Joanna Masel2

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Summary
This summary is machine-generated.

New proteins can arise from noncoding DNA, supported by the "preadapting selection" hypothesis. This suggests that even error-translated sequences can be shaped by natural selection, particularly when errors are frequent.

Keywords:
de novo gene birthevolvabilityphenotypic mutationpreadaptationstop codon readthroughtranslation error

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Area of Science:

  • Genetics
  • Molecular Biology
  • Evolutionary Biology

Background:

  • De novo protein evolution from noncoding DNA challenges expectations due to likely deleterious effects of random translation.
  • The "preadapting selection" hypothesis proposes that low-level, error-driven translation of noncoding DNA precedes its co-option into functional genes.
  • This hypothesis predicts that selection on error-translated polypeptides is stronger when erroneous expression is higher.

Purpose of the Study:

  • To investigate the role of readthrough translation errors in the emergence of new protein-coding genes from noncoding DNA.
  • To test the "preadapting selection" hypothesis by examining noncoding sequences downstream of stop codons in Saccharomyces cerevisiae.

Main Methods:

  • Analysis of noncoding sequences downstream of stop codons in Saccharomyces cerevisiae.
  • Identification of "fragile" proteins under selection to minimize readthrough.
  • Assessment of readthrough translation using ribosome profiling data.
  • Evaluation of intrinsic structural disorder in C-terminal extensions.

Main Results:

  • A subset of "fragile" proteins under strong selection against readthrough were identified as unlikely substrates for co-option.
  • Noncoding sequences showing evidence of readthrough translation encoded C-terminal extensions with higher intrinsic structural disorder.
  • This higher disorder was primarily attributed to the cryptic sequences beyond the stop codon, not spillover effects.
  • Results remained robust after controlling for selection strength and C-terminal extension length.

Conclusions:

  • The findings support the "preadapting selection" hypothesis, indicating selection acts on 3' UTRs to purge deleterious cryptic polypeptides.
  • Selection on these cryptic polypeptides is stronger in genes with higher rates of readthrough errors.
  • This provides evidence for selection shaping noncoding DNA through error-prone translation, facilitating de novo gene evolution.