Viral Dark Matter: Evolution and Impact in Phage Biology

The rapid expansion of high-throughput sequencing and viral metagenomics has uncovered a vast and largely uncharacterized reservoir of viral genetic diversity, commonly termed “viral dark matter.” This concept encompasses viral sequences that lack functional annotation, taxonomic classification, or detectable homology to known genes, and are therefore largely absent from current reference databases. Within phage biology, viral dark matter constitutes both a significant analytical challenge and a unique opportunity to reveal previously unrecognized dimensions of bacteriophage evolution, ecology, and function.

This Research Topic examines the origins, evolution, and biological significance of viral dark matter, with particular emphasis on bacteriophages and their interactions with bacterial, archaeal, protist, and fungal hosts. It seeks to contextualize the emergence of viral dark matter within the historical development of viral metagenomics, highlighting key advances in sequencing technologies and bioinformatics methods that have facilitated the discovery of novel viral lineages, expanding the known boundaries of the virosphere.

A central objective is to bridge the gap between sequence discovery and functional interpretation. Many phage genomes and metagenomic assemblies contain a high proportion of hypothetical proteins, which constrains our ability to translate genomic resources into a mechanistic understanding of viral biology. Contributions that address the structural and functional characterization of these unknown genes are particularly encouraged, as are studies employing comparative genomics, codon usage analyses, and compositional bias assessments to infer evolutionary pressures and host adaptation strategies. Emerging AI and structural biology approaches may further shed light on assigning functions to genes in the pool of dark matter.

This Research Topic also welcomes investigations into cryptic and mobile genetic elements, including prophages, plasmid-like phages, and other entities that blur the distinction between viruses and cellular genomes. Studies addressing phage–host co-evolution, anti-CRISPR systems, horizontal gene transfer, and the role of viral dark matter in shaping microbial communities, antimicrobial resistance dissemination, and virulence are especially relevant. In addition, submissions engaging with the ongoing debates surrounding the classification, ecological roles, and evolutionary trajectories of these enigmatic viral entities are strongly encouraged.

Methodological innovation is equally critical. This Research Topic invites contributions presenting novel computational, statistical, and experimental approaches for the detection, annotation, and functional validation of viral dark matter. Studies spanning environmental, clinical, and engineered microbiomes are welcome, with the aim of providing a comprehensive and integrative perspective on hidden viral diversity and ecology. By integrating historical context, technological innovation, and cutting-edge biological insights, this Research Topic aims to advance understanding of viral dark matter and its far-reaching implications for phage biology, microbial evolution, and ecosystem function.

In this collection we welcome contributions on the following sub-themes (but not limited to), as they relate to furthering our knowledge of viral dark matter:

● Discovery and characterization of viral dark matter
● Evolutionary origins and dynamics of viral dark matter
● Classification, taxonomy, and conceptual frameworks
● Functional annotation of phages and their biological roles
● Phage–host interactions and co-evolution
● Ecological and environmental impacts of phages
● Therapeutic, biocontrol, food safety, environmental safety, and other applications of phages
● Methodological and technological innovations
● Historical and conceptual development of phage research
● Integrative and systems-level perspectives on phages

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description: FAIR² DATA Direct Submission, FAIR² Data, Hypothesis and Theory, Methods, Mini Review, Opinion, Original Research, Perspective, Review, Systematic Review, Technology and Code.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Viral dark matter, Bacteriophages, Viral metagenomics, Mobile genetic elements, Phage–host interactions, Functional annotation

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.