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Archaic Introgression Shapes Genetic Variation at Loci Associated With DNA Virus Load in Modern Humans.

Rutvi Rajpara1, Sofiia Stefaniia Polishchuk1, Danat Yermakovich1

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Summary
This summary is machine-generated.

Ancient DNA from Neandertals and Denisovans influences modern human immunity to DNA viruses. These archaic genetic contributions, particularly impacting Epstein-Barr virus (EBV) loads, reveal new insights into host-pathogen evolution.

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archaic admixturehost–pathogen interactionhuman evolutionimmune response

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Area of Science:

  • Human evolutionary genetics
  • Immunology
  • Virology

Background:

  • Archaic introgression has shaped human immunity, especially RNA virus responses.
  • The role of archaic DNA in DNA virus defense is largely unknown.

Purpose of the Study:

  • Investigate Neandertal and Denisovan haplotype contributions to DNA virus loads.
  • Analyze genome-wide associations with five common DNA viruses in UK Biobank data.

Main Methods:

  • Genome-wide association study (GWAS) using summary statistics.
  • Analysis of UK Biobank data for DNA virus loads.
  • Identification of significant associations and haplotype analysis.

Main Results:

  • 18 genome-wide significant associations found, mainly for Epstein-Barr virus (EBV) and within the Major Histocompatibility Complex.
  • A Denisovan-like haplotype linked to HLA-A*11:01 showed increased EBV loads.
  • Two chromosome 17 haplotypes associated with higher EBV loads exhibited phenotypic and functional effects on immune genes.

Conclusions:

  • Archaic DNA systematically impacts modern human DNA virus immunity.
  • These effects differ from previously identified RNA virus associations.
  • Findings offer evolutionary and functional insights into archaic admixture and antiviral defense.