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Nullomers and High Order Nullomers in Genomic Sequences.

Davide Vergni1, Daniele Santoni2

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Nullomers, absent DNA words, are more numerous in genomes than random chance suggests. Their unique structure, including CpG content and helical rise, indicates they are a peculiar genomic feature, not just statistical anomalies.

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Area of Science:

  • Genomics
  • Bioinformatics
  • Computational Biology

Background:

  • Nullomers are DNA oligomers absent as subsequences in a given DNA sequence.
  • Their significance in drug discovery and forensic science is under investigation.
  • The origin of nullomers—statistical or peculiar genomic feature—remains debated.

Purpose of the Study:

  • Investigate the nature of nullomers and their prevalence in genomic sequences.
  • Introduce and study high order nullomers, which remain nullomers after mutation.
  • Explore the structural and evolutionary properties of nullomers.

Main Methods:

  • Compared nullomer counts in the human genome versus random sequences.
  • Analyzed CpG distribution and dinucleotide frequencies within nullomers.
  • Calculated mean helical rise for nullomer sequences.
  • Constructed phylogenetic trees based on nullomer sharing and dinucleotide frequencies across eleven species.

Main Results:

  • The human genome contains significantly more nullomers than expected by chance.
  • Nullomers exhibit distinct CpG frequencies dependent on dinucleotide position, suggesting a unique structure.
  • Nullomers are conserved among closely related species.
  • Nullomer sequences display high mean helical rise, indicating peculiar structural features.

Conclusions:

  • Nullomers arise from the intrinsic structural properties of DNA, including CpG frequency bias and CpG islands.
  • The hypermutability model, even with CpG islands, is insufficient to explain the nullomer phenomenon.
  • High order nullomers may enhance the utility of simple nullomers in various applications.