Small viruses reveal bidirectional evolution between HK97-fold viruses and encapsulins via procapsids

The HK97-fold is an ancient, conserved protein structure that forms protein shells. It is the building block of capsids that protect the genome of viruses in the Duplodnaviria realm, infecting organisms across all domains of life. It is also the building block of encapsulins, compartments that confine biochemical reactions in prokaryotes. Recent genomic studies have hypothesized that encapsulins evolved from HK97-fold viruses. However, this evolutionary pathway is challenging to justify biophysically because HK97-fold viruses form larger and more complex protein shells than encapsulins. We addressed this paradox by searching for smaller and simpler HK97-fold viral capsids across ecosystems. The investigation yielded a well-defined group of viral entities, which encode HK97-fold proteins displaying molecular similarities with encapsulins and lacking portal and tail genes. The structural phylogenetic analysis of HK97-fold entities revealed bidirectional evolutionary transitions between encapsulins and HK97-fold viruses. An evolutionary mechanism responsible for such transitions was proposed based on the presence of lysogeny-associated genes in the viral entities and the structural and molecular parallels between encapsulins and procapsids, the immature state of viral capsids before genome packaging. We concluded that procapsids are akin to the common HK97-fold protein shell ancestor and might still facilitate transitions between modern viruses and encapsulins. The potential genomic and biochemical functions of HK97-fold procapsids make them an ideal candidate model for the early evolution of life and might require a revision of the role of viral capsids in the biosphere.