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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Regulatory activity is the default DNA state in eukaryotes.

Ishika Luthra1, Cassandra Jensen1, Xinyi E Chen1

  • 1School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada.

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Summary

Most DNA sequences are transcribed, but functional genes show evidence of selection. This study reveals that basal regulatory activity is common, with selection shaping specific functions or repressing detrimental elements.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Genomes contain both genes and non-coding DNA with transcriptional potential.
  • Transcripts from non-coding DNA often lack conservation and clear function, raising questions about biological noise.

Purpose of the Study:

  • To quantify the regulatory activity of evolutionarily naive DNA in yeast and humans.
  • To determine the extent of biological noise from non-genic sequences.
  • To investigate the role of evolutionary selection in shaping transcriptional activity.

Main Methods:

  • RNA sequencing (RNA-seq) in yeast to analyze naive DNA transcription.
  • Computational predictions in humans to assess chromatin activity in naive DNA.
  • Comparison of naive and evolved DNA regulatory patterns.

Main Results:

  • Over 99% of naive DNA bases were transcribed in yeast, often with overlapping transcripts.
  • Human naive DNA shows predicted chromatin activity similar to evolved DNA in some aspects.
  • Extreme transcriptional activities were rare in naive DNA, suggesting selection's role.

Conclusions:

  • Basal regulatory activity appears to be the default state for DNA.
  • Evolutionary selection refines this activity for function or represses detrimental elements.
  • Coherent gene structures are favored by selection, as evidenced by transcript overlap patterns.