{
  "abstract": "Housekeeping genes are commonly defined as broadly expressed genes that support essential cellular function. However, their identification in genome-wide datasets typically relies on spatial variation across adult tissues, while largely overlooking developmental time as an additional dimension of gene expression diversity. Here, we systematically compare gene expression breadth across developmental stages and adult tissues using zebrafish (Danio rerio) transcriptomic datasets that span embryogenesis and differentiated tissues. We classify genes according to their temporal expression breadth during development and examine how these patterns relate to traditional tissue-based definitions of housekeeping genes. As expected, developmental and adult expression breadth show only partial concordance: while a core set of genes is broadly expressed across both dimensions, many genes that are ubiquitous across adult tissues exhibit restricted expression during embryogenesis, and some genes expressed throughout development later become tissue-specific. Genes expressed across all developmental stages are enriched for fundamental cellular processes, show strong evolutionary conservation, and are associated with highly pleiotropic phenotypes. Notably, genes expressed during restricted developmental windows—particularly around gastrulation—can also play essential roles. These results highlight that expression ubiquity depends on both temporal and spatial context and underscore the importance of considering both dimensions explicitly when identifying and interpreting broadly expressed genes. More broadly, our analysis provides a framework for comparing developmental and tissue expression breadth and for exploring how gene expression dynamics across the life cycle relate to functional and evolutionary constraints. Author summary: Genes that are active in many conditions are called housekeeping genes. These genes are usually identified from adult tissues, because such data are the most widely available. However, this overlooks how gene activity changes during early development, leaving an incomplete picture of what it means for a gene to be broadly expressed. In this study, using zebrafish as a model, we compare how widely genes are expressed over time during embryonic development and across adult organs. These two patterns only partly overlap. Some genes are active throughout development, while others are widely expressed in adult tissues but only active during specific developmental stages, or vice versa. We show that genes active across all stages tend to carry out essential cellular roles, are highly conserved across species, and have widespread effects when disrupted. In contrast, genes with more limited activity are often involved in controlling specific developmental processes. Our findings demonstrate that developmental and adult tissue expression capture complementary aspects of gene ubiquity. This broader view helps clarify gene function across the life cycle.",
  "abstract_shown": true,
  "affiliations": [
    "Centro Nacional de Biotecnologia (CNB-CSIC), Madrid, Spain",
    "Museo Nacional de Ciencias Naturales (MNCN-CSIC), Madrid, Spain",
    "Centro de Neurociencias Cajal (CNC-CSIC), Madrid, Spain"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alicia Lou"
    },
    {
      "affs": [
        1
      ],
      "name": "Juan F. Poyatos"
    },
    {
      "affs": [
        2
      ],
      "name": "Monica Chagoyen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2hm8mvk02rb15.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pcbi.1014787",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014787",
  "id": "2hm8mvk02rb15",
  "issns": [
    "1553-7358"
  ],
  "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014787",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Developmental Biology and Gene Regulation"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Genome analysis/Gene ontologies"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Genome analysis/Transcriptome analysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Evolutionary developmental biology"
    ],
    [
      "plos",
      "/Biology and life sciences/Evolutionary biology/Evolutionary developmental biology"
    ],
    [
      "plos",
      "/Biology and life sciences/Evolutionary biology/Evolutionary genetics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome analysis/Gene ontologies"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome analysis/Transcriptome analysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Phenotypes"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Animals/Vertebrates/Fish/Osteichthyes/Zebrafish"
    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Animals/Vertebrates/Fish/Osteichthyes/Zebrafish"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Zebrafish"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Zebrafish"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Zebrafish"
    ]
  ],
  "openalex": "W7213937818",
  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014787&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/2hm8mvk02rb15.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pcbi.1014787",
      "source": "plos",
      "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014787"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:computational biology",
      "subfield": "bioinformatics"
    },
    {
      "field": "biology",
      "origin": "plos:evolutionary biology",
      "subfield": "evolutionary-biology"
    },
    {
      "field": "biology",
      "origin": "plos:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Developmental and tissue expression breadth define distinct but overlapping classes of housekeeping genes",
  "title_text": "Developmental and tissue expression breadth define distinct but overlapping classes of housekeeping genes",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/2hm8mvk02rb15",
  "venue": "PLOS Computational Biology",
  "versions": []
}