Viral speciation through subcellular genetic isolation and virogenesis incompatibility

Abstract

Understanding how biological species arise is critical for understanding the evolution of life on Earth. Bioinformatic analyses have recently revealed that viruses, like multicellular life, form reproductively isolated biological species. Viruses are known to share high rates of genetic exchange, so how do they evolve genetic isolation? Here, we evaluate two related bacteriophages and describe three factors that limit genetic exchange between them: 1) A nucleus-like compartment that physically separates replicating phage genomes, thereby limiting inter-phage recombination during co-infection; 2) A tubulin-based spindle that orchestrates phage replication and forms nonfunctional hybrid polymers; and 3) A nuclear incompatibility factor that reduces phage fitness. Together, these traits maintain species differences through Subcellular Genetic Isolation where viral genomes are physically separated during co-infection, and Virogenesis Incompatibility in which the interaction of cross-species components interferes with viral production.

The Phage Nucleus and PhuZ Spindle: Defining Features of the Subcellular Organization and Speciation of Nucleus-Forming Jumbo Phages

“…For example, PhuZ proteins of phage PhiKZ and PhiPA3 share limited sequence identity (37%), yet they co-assemble to form a hybrid filament during co-infection. However, the hybrid PhiKZ-PhiPA3 filament has lost all dynamic properties, and thus is non-functional (Chaikeeratisak et al, 2021;Figure 2B). Since the PhuZ spindle plays many crucial roles in phage development such as nuclear positioning (Kraemer et al, 2012;Erb et al, 2014;Chaikeeratisak et al, 2017b), nuclear rotation (Chaikeeratisak et al, 2017b(Chaikeeratisak et al, , 2019, and capsid trafficking (Chaikeeratisak et al, 2019), the hybrid filaments interfere with the replication of both infecting species, which results in smaller and mispositioned nuclei, and a ∼ 50% decrease in the number of phage offspring (Chaikeeratisak et al, 2019(Chaikeeratisak et al, , 2021.…”

“…Viruses are known to have very high rates of genetic exchange that can occur when two phages infect the same host cell ( Bobay and Ochman, 2018 ; Chaikeeratisak et al, 2021 ). Recent studies suggest co-infections of bacteria are very common in natural ecosystems ( Díaz-Muñoz, 2017 ; Luque and Silveira, 2020 ).…”

“…Host specificity is therefore known to be one of the key factors that limits genetic exchange among two phages and allows two strains to diverge from one another ( Duffy et al, 2007 ; Meyer et al, 2016 ; Saxenhofer et al, 2019 ). We recently studied nucleus-forming jumbo phages and discovered several speciation factors belonging to two general mechanisms of viral speciation ( Chaikeeratisak et al, 2021 ; Figure 2 ). First, we found that the proteinaceous shell which guards phage genetic material from host immunity also forms a barrier that reduces the likelihood of genetic exchange between phages during co-infection ( Figure 2A ).…”

“…This subcellular isolation also occurred when the cell was co-infected with a single species of phage (either PhiKZ or PhiPA3). The phage nucleus thus establishes “Subcellular Genetic Isolation,” a condition limiting the opportunity for co-infecting viruses to recombine due to subcellular spatial restrictions ( Chaikeeratisak et al, 2021 ; Figure 2A ). Subcellular Genetic Isolation is likely a widespread mechanism that limits genetic exchange among viruses and therefore contributes to their species diversity ( Schmid et al, 2014 ).…”

“…(B) Virogenesis Incompatibility occurs when divergent components of phage replication interact negatively, causing interference with viral replication, such as PhuZ (a cytoplasmic speciation factor) and gp210 (a nuclear speciation factor). This incompatibility results in a reduction in phage fitness ( Chaikeeratisak et al, 2021 ).…”