Diversity and evolution of prokaryotic viral lytic proteins

Lytic proteins, essential for viral life cycles, mediate cell lysis, driving nutrient, and gene flow in ecosystems. Despite advances in understanding viral lysis mechanisms, the lytic proteins of prokaryotic viruses remain poorly understood at the macroevolutionary scale. Here, we constructed the Prokaryotic DNA Virus Lytic Protein Dataset, revealing the diversity, distribution patterns, and evolutionary drivers of lytic proteins across viral genomes. Our results demonstrate sequence and structural variation, suggesting that the composition of the lysis system is closely linked to viral genome size, host cell wall structure, and lifestyle, reflecting ecological adaptation. We observed that viral lytic proteins exhibit extensive sequence variation but retain structural conservation, suggesting a stronger selective pressure on structure that may be driven by the need to adapt and conform with specific cell envelope architectures. Phylogenetic analyses identified a significant co-evolutionary signal among lytic proteins, alongside extensive horizontal gene transfer of endolysin and holin encoding genes between bacteriophages and bacteria. These analyses also support that viral lytic proteins likely originated from bacterial sources, with different functional types having multiple independent origins. Moreover, comparative analysis of DNA and RNA virus lytic proteins demonstrates their diversity and differences across viral lineages. Revealing vast unexplored lytic proteins diversity, this study highlights their biotechnological potential against multidrug-resistant pathogens.