Comparative metagenomic analyses reveal viral-induced shifts of host metabolism towards nucleotide biosynthesis (In collaboration with Prof. Oded Beja)
Background: Viral genomes often contain metabolic genes that were acquired from host genomes (auxiliary genes). It is assumed that these genes are fixed in viral genomes as a result of a selective force, favoring viruses that acquire specific metabolic functions. While many individual auxiliary genes were observed in viral genomes and metagenomes, there is great importance in investigating the abundance of auxiliary genes and metabolic functions in the marine environment towards a better understanding of their role in promoting viral reproduction.
Results: In this study, we searched for enriched viral auxiliary genes and mapped them to metabolic pathways. To initially identify enriched auxiliary genes, we analyzed metagenomic microbial reads from the Global Ocean Survey (GOS) dataset that were characterized as viral, as well as marine virome and microbiome datasets from the Line Islands. Viral-enriched genes were mapped to a “global metabolism network” that comprises all KEGG metabolic pathways. Our analysis of the viral-enriched pathways revealed that purine and pyrimidine metabolism pathways are among the most enriched pathways. Moreover, many other viral-enriched metabolic pathways were found to be closely associated with the purine and pyrimidine metabolism pathways. Furthermore, we observed that sequential reactions are promoted in pathways having a high proportion of enriched genes. In addition, these enriched genes were found to be of modular nature, participating in several pathways.
Conclusions: Our naïve metagenomic analyses strongly support the well-established notion that viral auxiliary genes promote viral replication via both degradation of host DNA and RNA as well as a shift of the host metabolism towards nucleotide biosynthesis, clearly indicating that comparative metagenomics can be used to understand different environments and systems without prior knowledge of pathways involved.
Hypergeometric enrichment analysis of the number of steps connecting each metabolic pathway to purine and pyrimidine metabolism pathways. (A)Red circle represents the purine and pyrimidine metabolism pathways. Lower numbers represent the path length to the purine and pyrimidine metabolism. Upper numbers represent the hypergeometric Pvalue for viral enrichment in each path length. Black-white scale colors correspond to hypergeometricPvalues. (B)Path length distribution for the viral-enriched and non-enriched metabolic pathways.