Evolutionary selection against short nucleotide sequences in viruses and their related hosts

Yoram Zarai, Zohar Zafrir, Bunpote Siridechadilok, Amporn Suphatrakul, Modi Roopin, Justin Julander, Tamir Tuller

Research output: Contribution to journalArticlepeer-review


Viruses are under constant evolutionary pressure to effectively interact with the host intracellular factors, while evading its immune system. Understanding how viruses co-evolve with their hosts is a fundamental topic in molecular evolution and may also aid in developing novel viral based applications such as vaccines, oncologic therapies, and anti-bacterial treatments. Here, based on a novel statistical framework and a large-scale genomic analysis of 2,625 viruses from all classes infecting 439 host organisms from all kingdoms of life, we identify short nucleotide sequences that are under-represented in the coding regions of viruses and their hosts. These sequences cannot be explained by the coding regions' amino acid content, codon, and dinucleotide frequencies. We specifically show that short homooligonucleotide and palindromic sequences tend to be under-represented in many viruses probably due to their effect on gene expression regulation and the interaction with the host immune system. In addition, we show that more sequences tend to be under-represented in dsDNA viruses than in other viral groups. Finally, we demonstrate, based on in vitro and in vivo experiments, how under-represented sequences can be used to attenuated Zika virus strains.

Original languageEnglish
Article numberdsaa008
JournalDNA Research
Issue number2
StatePublished - 19 May 2020


  • Zika virus
  • systems-biology
  • under-represented sequences
  • virus-host co-evolution


Dive into the research topics of 'Evolutionary selection against short nucleotide sequences in viruses and their related hosts'. Together they form a unique fingerprint.

Cite this