Evidence map›Paper›PMID 38977308›Full record

ArticleGenome research2024

Large-scale investigation of species-specific orphan genes in the human gut microbiome elucidates their evolutionary origins.

Nikolaos Vakirlis, Anne Kupczok

Abstract read
In one paragraph

Article in Genome research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Imported, not invented, genes prevail amongProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Something from nothing: The birth of new phage defense genes.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Emergence of antiphage functions from random sequence libraries reveals mechanisms of gene birth.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Orphan genes are not a distinct biological entity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Nikolaos VakirlisInstitute For Fundamental Biomedical Research, B.S.R.C. "Alexander Fleming," Vari 166 72, Greece; vakirlis@fleming.gr anne.kupczok@wur.nl.ORCID 0000-0001-7606-6987
Anne KupczokBioinformatics Group, Wageningen University, 6700 PB Wageningen, The Netherlands vakirlis@fleming.gr anne.kupczok@wur.nl.ORCID 0000-0001-5237-1899

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Species-specific genes, also known as orphans, are ubiquitous across life's domains. In prokaryotes, species-specific orphan genes (SSOGs) are mostly thought to originate in external elements such as viruses followed by horizontal gene transfer, whereas the scenario of native origination, through rapid divergence or de novo, is mostly dismissed. However, quantitative evidence supporting either scenario is lacking. Here, we systematically analyzed genomes from 4644 human gut microbiome species and identified more than 600,000 unique SSOGs, representing an average of 2.6% of a given species' pangenome. These sequences are mostly rare within each species yet show signs of purifying selection. Overall, SSOGs use optimal codons less frequently, and their proteins are more disordered than those of conserved genes (i.e., non-SSOGs). Importantly, across species, the GC content of SSOGs closely matches that of conserved ones. In contrast, the ∼5% of SSOGs that share similarity to known viral sequences have distinct characteristics, including lower GC content. Thus, SSOGs with similarity to viruses differ from the remaining SSOGs, contrasting an external origination scenario for most of them. By examining the orthologous genomic region in closely related species, we show that a small subset of SSOGs likely evolved natively de novo and find that these genes also differ in their properties from the remaining SSOGs. Our results challenge the notion that external elements are the dominant source of prokaryotic genetic novelty and will enable future studies into the biological role and relevance of species-specific genes in the human gut.

Indexed as

Evolution, MolecularGastrointestinal MicrobiomeSpecies SpecificityBase CompositionHumansPhylogeny

Identifiers

PMID38977308
PMCPMC11293555

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.