The Coevolution Of Large And Small Terminases Of Bacteriophages Is A Result Of Purifying Selection Leading To Phenotypic Stabilization

Genome packaging in many dsDNA phages requires a series of precisely coordinated actions of two phage-coded proteins, namely, large terminase (TerL) and small terminase (TerS) with DNA and ATP, and with each other. Despite the strict functional conservation, TerL and TerS homologs exhibit large sequence variations. We investigated the sequence variability across eight phage types and observed a coevolutionary framework wherein the genealogy of TerL homologs mirrored that of the corresponding TerS homologs. Furthermore, a high purifying selection observed (dN/dS << 1) indicated strong structural constraints on both TerL and TerS, and identify coevolving residues in TerL and TerS of phage T4 and lambda. Using the highly coevolving (correlation coefficient of 0.99) TerL and TerS of phage N4, we show that their biochemical features are similar to the phylogenetically divergent phage lambda terminases. We also demonstrate using the Surface Plasma Resonance (SPR) technique that phage N4 TerL transiently interacts with TerS.