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Genome-wide Surveillance of Transcription Errors in Eukaryotic Organisms
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Transcript diversity reflects deleterious RNA processing errors shaped by population size in metazoans.

Kai Mi1, Lili Guan1,2, Bandhan Sarker1

  • 1Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.

Plos Biology
|April 16, 2026
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Summary
This summary is machine-generated.

Transcript diversity from alternative transcription initiation, splicing, and polyadenylation is largely detrimental. This diversity decreases with larger population sizes, supporting an error hypothesis over an adaptive one.

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Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Genomics

Background:

  • Eukaryotic genes generate diverse transcripts via alternative transcription initiation (ATI), alternative splicing (AS), and alternative polyadenylation (APA).
  • The biological significance of this transcript diversity is debated, with hypotheses suggesting it is either adaptive or largely deleterious due to molecular errors.

Purpose of the Study:

  • To investigate the role of effective population size (Ne) in shaping transcript diversity.
  • To test the prediction that transcript diversity declines with increasing Ne, as predicted by the error hypothesis.

Main Methods:

  • Analysis of 166 transcriptomes from 75 metazoan species.
  • Quantification of transcript diversity using the percentage of minor ATI, AS, and APA sites.
  • Correlation analysis between transcript diversity metrics and Ne or its proxies.

Main Results:

  • Transcript diversity, measured by the usage of minor ATI, AS, and APA sites, significantly decreases with increasing effective population size (Ne).
  • This inverse correlation was observed across a diverse range of metazoan species.

Conclusions:

  • The findings support the error hypothesis, suggesting that transcript diversity is largely a byproduct of molecular errors in transcription and RNA processing.
  • Natural selection is more effective at minimizing these errors in species with larger effective population sizes, leading to reduced transcript diversity.