Functional Unknomics of the SAR11 clade using bioinformatics approaches

A substantial fraction of the genes in marine bacteria lack detectable sequence similarity to genes with known functions. These functionally uncharacterized genes--collectively referred to as the "unknome"--represent a largely unexplored genetic repertoire harboring insights into marine bacterial ecology. In this study, we explored the function of the unknome of SAR11 clade, the most abundant bacterial lineage in the ocean, with a particular focus on genes that provide insight into their ecology. Based on the COG classification, approximately 58% of SAR11 ortholog groups were classified as unknome. Among the SAR11 unknome, we successfully inferred the functions of 69 ortholog groups that are conserved in SAR11 clade by protein structure similarity searches and genomic context analyses. These ortholog groups include putative transporter components, supporting the current ecological understanding that SAR11 clade is specialized in substrate uptake to adapt to oligotrophic marine environments. Furthermore, structural analysis indicated that the DUF2237-containing protein, enriched in marine environments, has potential interactions with purine nucleotide-containing compounds. This may suggest the existence of unique nucleotide utilization mechanisms in marine bacteria. In addition, we found candidates of virus defense systems within the unknome, which demonstrates that diverse defense systems are present at least in one-third of the cultured SAR11 strains. The conservation of these viral defense systems, even within streamlined SAR11 genomes, suggests that they confer significant ecological advantages. Our exploration provided insights into the genetic basis of bottom-up processes (adaptation to oligotrophic environments) and top-down processes (antiviral defense strategy) contributing to ecological success of SAR11.