Cyanobacteria-cyanophage interactions between freshwater and marine ecosystems based on large-scale cyanophage genomic analysis

The disparities in harmful algal blooms dynamics are largely attributed to variations in cyanobacteria populations within aquatic ecosystems. However, cyanobacteria-cyanophage interactions and their role in shaping cyanobacterial populations has been previously underappreciated. To address this knowledge gap, we isolated and sequenced 42 cyanophages from diverse water sources in China, with the majority (n = 35) originating from freshwater sources. We designated these sequences as the "Novel Cyanophage Genome sequence Collection" (NCGC). NCGC displayed notable genetic variations, with 95% (40/42) of the sequences representing previously unidentified taxonomic ranks. By integrating NCGC with public data of cyanophages and cyanobacteria, we found evidence for more frequent historical cyanobacteria-cyanophage interactions in freshwater ecosystems. This was evidenced by a higher prevalence of prophage integrase-related genes in freshwater cyanophages (37.97 %) than marine cyanophages (7.42 %). In addition, freshwater cyanophages could infect a broader range of cyanobacteria orders (n = 4) than marine ones (n = 0). Correspondingly, freshwater cyanobacteria harbored more defense systems per million base pairs in their genomes, indicating more frequent phage infections. Evolutionary and cyanophage epidemiological studies suggest that interactions between cyanobacteria and cyanophages in freshwater and marine ecosystems are interconnected, and that brackish water can act as a transitional zone for freshwater and marine cyanophages. In conclusion, our research significantly expands the genetic information database of cyanophage, offering a wider selection of cyanophages to control harmful cyanobacterial blooms. Additionally, we represent a pioneering large-scale and comprehensive analysis of cyanobacteria and cyanophage sequencing data, and it provides theoretical guidance for the application of cyanophages in different environments.