{
  "abstract": "Paralogous compensation drives genetic robustness; however, its in vivo prevalence in humans and the evolutionary forces shaping it remain unresolved. We CRISPR-screened 678 human paralog pairs to identify pairs with negative genetic interactions (nGIs) or compensatory paralogs, and integrated our results with four studies to assemble two complementary resources: the 2168-pair Union and 4859-pair Ito datasets. We extrapolated to the organismal level by classifying paralogs as core (broadly compensating, 99 Union/120 Ito pairs), conditional (111/566) or non-interacting (1958/4173), and testing for enriched compensatory signals in core pairs relative to the latter two groups. Core nGI pairs consistently showed prenatal co-expression, depletion of disease genes and enrichment for upregulation after paralog loss in cancer, though the signals were often moderate. Evolutionary analyses found similar fractions (∼2%) of core compensators among both ancient and young paralogs. Ancient pairs retain overlaps likely under pleiotropic and dosage constraints. Incomplete small-scale duplication mechanisms limit compensation among young pairs, except X-derived retrogenes, which are overrepresented among core nGIs (∼14%). This is consistent with selection to counteract male germline X inactivation and subsequent out-of-testis expansion. Overall, paralogous compensation is moderately prevalent in vivo in humans, shaped by multiple evolutionary forces acting on ancient or young duplicates.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.",
    "University of Chinese Academy of Sciences, Beijing 100049, China.",
    "State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.",
    "State Key Laboratory of Complex, Severe, and Rare Diseases, Center for Bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.",
    "Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.",
    "Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jieyu Shen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Daqi Yu"
    },
    {
      "affs": [
        2
      ],
      "name": "Wenjia Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tianhan Su",
      "orcid": "0000-0001-7635-1729"
    },
    {
      "affs": [
        2
      ],
      "name": "Dingding Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Junbo Liang"
    },
    {
      "affs": [
        3
      ],
      "name": "Yiqiong Guo"
    },
    {
      "affs": [
        3
      ],
      "name": "Shangqi Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Huijing Ma"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Jichang Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiaoyue Wang",
      "orcid": "0000-0002-0208-5322"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yong E Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/77sf8bpb4d1gd.bib",
  "cited_by": 0,
  "doi": "10.1093/nsr/nwag565",
  "fulltext_url": "https://europepmc.org/articles/PMC13715443",
  "id": "77sf8bpb4d1gd",
  "issns": [
    "2095-5138",
    "2053-714X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953730",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/MED00010"
    ],
    [
      "heading",
      "AcademicSubjects/SCI00010"
    ],
    [
      "heading",
      "Molecular Biology & Genetics"
    ],
    [
      "heading",
      "Nsr/8"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1110|Chromosomal and Genetic Variations"
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  "openalex": "W7207835417",
  "pdf_url": "https://europepmc.org/articles/PMC13715443?pdf=render",
  "pmcid": "PMC13715443",
  "pmid": "42953730",
  "published": "2026-09-03",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/77sf8bpb4d1gd.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953730",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953730"
    },
    {
      "first_seen": "2026-11-01T12:22:44Z",
      "native_id": "PMC13715443",
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      "url": "https://doi.org/10.1093/nsr/nwag565"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1110|Chromosomal and Genetic Variations",
      "subfield": "plant-biology"
    }
  ],
  "title": "Moderate prevalence and evolutionary causes of paralogous compensation in humans.",
  "title_text": "Moderate prevalence and evolutionary causes of paralogous compensation in humans.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:44Z",
  "url": "https://research.draconitic.com/paper/77sf8bpb4d1gd",
  "venue": "National science review",
  "versions": []
}