A Depletion of Stop Codons in lincRNA is Owing to Transfer of Selective Constraint from Coding Sequences

Liam Abrahams, Laurence D. Hurst

Research output: Contribution to journalArticlepeer-review

1 Citation (SciVal)


Although the constraints on a gene's sequence are often assumed to reflect the functioning of that gene, here we propose transfer selection, a constraint operating on one class of genes transferred to another, mediated by shared binding factors. We show that such transfer can explain an otherwise paradoxical depletion of stop codons in long intergenic noncoding RNAs (lincRNAs). Serine/arginine-rich proteins direct the splicing machinery by binding exonic splice enhancers (ESEs) in immature mRNA. As coding exons cannot contain stop codons in one reading frame, stop codons should be rare within ESEs. We confirm that the stop codon density (SCD) in ESE motifs is low, even accounting for nucleotide biases. Given that serine/arginine-rich proteins binding ESEs also facilitate lincRNA splicing, a low SCD could transfer to lincRNAs. As predicted, multiexon lincRNA exons are depleted in stop codons, a result not explained by open reading frame (ORF) contamination. Consistent with transfer selection, stop codon depletion in lincRNAs is most acute in exonic regions with the highest ESE density, disappears when ESEs are masked, is consistent with stop codon usage skews in ESEs, and is diminished in both single-exon lincRNAs and introns. Owing to low SCD, the maximum lengths of pseudo-ORFs frequently exceed null expectations. This has implications for ORF annotation and the evolution of de novo protein-coding genes from lincRNAs. We conclude that not all constraints operating on genes need be explained by the functioning of the gene but may instead be transferred owing to shared binding factors.

Original languageEnglish
Pages (from-to)1148-1164
Number of pages17
JournalMolecular Biology and Evolution
Issue number4
Early online date16 Dec 2019
Publication statusPublished - 1 Apr 2020


  • ESE
  • exonic splice enhancer
  • lincRNA
  • sequence evolution
  • stop codon
  • transfer selection

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


Dive into the research topics of 'A Depletion of Stop Codons in lincRNA is Owing to Transfer of Selective Constraint from Coding Sequences'. Together they form a unique fingerprint.

Cite this