Zeta CrAss-like Phages, a Separate Phage Family Using a Variety of Adaptive Mechanisms to Persist in Their Hosts.

Bacteriophages of the order Crassvirales are highly abundant and near-universal members of the human gut microbiome worldwide. Zeta crAss-like phages comprise a separate group in the order and their genomes exhibit greater variability than genomes of crAss-like phages from other families within the order. Zeta crAss-like phages employ multiple adaptation mechanisms, ensuring their survival despite host defenses and environmental pressure. Some Zeta crAss-like phages use alternative genetic coding and exploit diversity-generating retroelements (DGRs). These features suggest complex evolutionary relationships with their bacterial hosts, sustaining parasitic coexistence. Mutations in tail fiber proteins introduced by DGR can contribute to their adaptation to changes in the host cell surface and even expand the range of their hosts. In addition, the exchange of DNA polymerases via recombination makes it possible to overcome the bacterial anti-phage protection directed at these enzymes. Zeta crAss-like phages continuously adapt due to genetic diversification, host interaction tweaks, and counter-defense innovations, driving an evolutionary arms race with hosts. Based on the genome characteristics of the Zeta crAss-like phages, we propose to separate them into the family ("эчәк"-"intestines" in Tatar) following the tradition of using the word "intestines" in different languages, suggested previously.