{
  "abstract": "A substantial fraction of the genes in 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 the SAR11 clade, the most abundant bacterial lineage in the ocean, with a particular focus on genes that provide insight into its ecology. Based on the Clusters of Orthologous Genes and Kyoto Encyclopedia of Genes and Genomes classifications, approximately 56% of SAR11 ortholog groups were classified as members of the unknome. Among the SAR11 unknome, we successfully inferred the functions of 57 ortholog groups that are conserved in the SAR11 clade by protein structure similarity searches and genomic context analyses. These ortholog groups include putative transporter components, supporting the current ecological understanding that the 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, may interact with purine nucleotide-containing compounds. This may suggest the existence of unique nucleotide utilization mechanisms in marine bacteria. In addition, we identified candidate viral defense systems within the unknome, indicating that diverse defense systems are present in at least one-third of cultured SAR11 strains. The presence of these defense systems, even within streamlined SAR11 genomes, suggests that they confer significant ecological advantages. Our analyses provide insights into the genetic basis of bottom-up processes (adaptation to oligotrophic environments) and top-down processes (antiviral defense strategy) contributing to ecological success.\n\nIMPORTANCE: Many microbial genes have no experimentally established function, limiting our ability to explain how microorganisms adapt to their environments. We examined this uncharacterized gene space, or “unknome” in SAR11, the most abundant bacterial clade in the ocean, by integrating evolutionary conservation, genomic context, predicted protein structure, and environmental distribution. This approach enabled us to prioritize components of the SAR11 unknome, including a core unknome conserved across the clade and genes enriched in specific lineages, and to identify several candidates with possible ecological roles in nutrient acquisition and defense against viruses. Our results suggest that the SAR11 unknome contains important clues to the ecological success of SAR11 rather than merely reflecting incomplete annotation or gene-prediction artifacts. Our study highlights the potential value of unknome analysis for identifying ecologically relevant genes in environmental microorganisms.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan",
    "Atmosphere and Ocean Research Institute, The University of Tokyo, Kashiwa, Chiba, Japan",
    "Department of Natural Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan",
    "RIKEN Pioneering Research Institute, Wako, Saitama, Japan",
    "Department of Life Science, College of Science, Rikkyo University, Toshima-ku, Tokyo, Japan",
    "Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Bunkyo-ku, Tokyo, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Satoshi Nishino",
      "orcid": "0009-0007-2070-7678"
    },
    {
      "affs": [
        2
      ],
      "name": "Kento Tominaga",
      "orcid": "0000-0003-4814-5690"
    },
    {
      "affs": [
        3
      ],
      "name": "Kimiho Omae",
      "orcid": "0009-0001-4033-5177"
    },
    {
      "affs": [
        4
      ],
      "name": "Teppei Deguchi",
      "orcid": "0009-0001-6340-3750"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Koji Hamasaki",
      "orcid": "0000-0002-8514-506X"
    },
    {
      "affs": [
        1,
        2,
        5
      ],
      "name": "Susumu Yoshizawa",
      "orcid": "0000-0001-9667-6010"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuki Nishimura",
      "orcid": "0000-0002-7990-1316"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ae28163p9vzcc.bib",
  "cited_by": 0,
  "doi": "10.1128/msystems.01026-26",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712998/",
  "id": "ae28163p9vzcc",
  "issns": [
    "2379-5077"
  ],
  "landing_url": "https://doi.org/10.1128/msystems.01026-26",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2303|Microbial Community Ecology and Physiology"
    ]
  ],
  "openalex": "W7213463780",
  "pdf_url": null,
  "pmcid": "PMC13712998",
  "pmid": "42752223",
  "published": "2026-09-17",
  "publisher": "American Society for Microbiology (ASM)",
  "ris": "https://research.draconitic.com/paper/ae28163p9vzcc.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:28Z",
      "native_id": "PMC13712998",
      "source": "pmc",
      "url": "https://doi.org/10.1128/msystems.01026-26"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2303|Microbial Community Ecology and Physiology",
      "subfield": "ecology"
    }
  ],
  "title": "Functional unknomics of the SAR11 clade reveal hidden genetic potential underlying adaptation to bottom-up and top-down pressures",
  "title_text": "Functional unknomics of the SAR11 clade reveal hidden genetic potential underlying adaptation to bottom-up and top-down pressures",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:28Z",
  "url": "https://research.draconitic.com/paper/ae28163p9vzcc",
  "venue": "mSystems",
  "versions": []
}