Ultraconserved bacteriophage genome sequence identified in 1300-year-old human palaeofaeces

Abstract

Bacteriophages are widely recognised as rapidly evolving biological entities. However, knowledge about ancient bacteriophages is limited. Here, we analyse DNA sequence datasets previously generated from ancient palaeofaeces and human gut-content samples, and identify an ancient phage genome nearly identical to present-day Mushuvirus mushu, a virus that infects gut commensal bacteria. The DNA damage patterns of the genome are consistent with its ancient origin and, despite 1300 years of evolution, the ancient Mushuvirus genome shares 97.7% nucleotide identity with its modern counterpart, indicating a long-term relationship between the prophage and its host. In addition, we reconstruct and authenticate 297 other phage genomes from the last 5300 years, including those belonging to unknown families. Our findings demonstrate the feasibility of reconstructing ancient phage genome sequences, thus expanding the known virosphere and offering insights into phage-bacteria interactions spanning several millennia.