FORMING GENOME TO PHENOME CONNECTIONS: BACTERIOPHAGE REPLICATION GENES
Date
2025-05
Authors
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Publisher
University of Delaware
Abstract
Viruses are the most genetically diverse and environmentally abundant
biological entities, however they are vastly understudied. Viral impacts on host
communities and ecosystems can be differentiated by distinct infection dynamics.
Lytic viruses lyse the host during infection, affecting nutrient cycling and community
composition. Temperate viruses incorporate their genomes into hosts during infection,
contributing to horizontal gene transfer and affecting host biology. DNA polymerase I
(PolA) is carried by many bacteriophages (bacterial viruses) and may be linked with
infection dynamics phenotypes. Variations in the PolA 526 residue (T7 numbering)
influence the speed and accuracy of DNA replication, a vital infection process. Three
previously identified 526 residues—phenylalanine, tyrosine, and leucine—influence
enzyme biochemistry and phage infection phenotypes. Faster replicating Phe526 or
Tyr526 PolAs tend to be found in lytic phage, while slower replicating Leu526 PolAs
are largely found in temperate phage. A novel histidine 526 variant has been identified
in oceanic viral metagenomes (viromes). In vitro biochemical analysis and in vivo
mutagenesis studies showed that His526 PolAs have hindered processivity and phage
T7 mutants encoding the His526 variant replicate slower. Bioinformatic analysis of
viromes show contextual differences in His526 PolAs that predominate in different
depths in oligotrophic ocean samples by sequence variation, as well as different
requirements for additional replication proteins. This study aims to strengthen the
PolA genome to phenome hypotheses and aid in predicting the infection strategies of
His526 viral populations to understand their impacts on ecosystem.