Evidence map›Paper›PMID 42202782›Full record

ArticleCell genomics2026

A protein interactome for the last eukaryotic common ancestor illuminates the biochemical basis of modern genetic diseases.

Rachael M Cox, Ophelia Papoulas, Shirlee Shril, Chanjae Lee, Tynan P Gardner, Zoya T Ansari, Anna M Battenhouse, Muyoung Lee, Kevin Drew, Claire D McWhite and 6 more

Abstract read
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In one paragraph

Article in Cell genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Rachael M CoxDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Ophelia PapoulasDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Shirlee ShrilDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Chanjae LeeDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Tynan P GardnerDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Zoya T AnsariDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Anna M BattenhouseDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Muyoung LeeDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Kevin DrewDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Claire D McWhiteDepartment of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA.
David YangDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Janelle C LeggereDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Dannie DurandDepartment of Biological Sciences, Carnegie Mellon University, 4400 5th Avenue, Pittsburgh, PA 15213, USA.
Friedhelm HildebrandtDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.
John B WallingfordDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Edward M MarcotteDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: marcotte@utexas.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

All eukaryotes share a single-celled ancestor from ∼1.5 to 1.8 billion years ago, the so-called last eukaryotic common ancestor (LECA). Roughly half of gene families found in modern eukaryotes were already present in LECA, forming molecular systems that continue to influence genetic diseases and traits today. To investigate these systems, we compared genes across 156 organisms to define a core set of protein-coding gene families likely present in LECA, with a quarter remaining uncharacterized. Integrating >26,000 mass spectrometry proteomics analyses from 31 species, we inferred higher-order complexes among these ancient proteins. This reconstructed interactome reveals both established and novel assemblies, offering a biochemical snapshot of LECA's organization. Finally, by exploring these ancient protein interactions, we found new human gene-disease associations for bone density and congenital birth defects, illustrating the value of ancestral protein networks for modern functional genetics.

Indexed as

EukaryotaGenetic Diseases, InbornProtein Interaction MapsAnimalsBone DensityEvolution, MolecularHumansProteomicsbone densityciliopathyevolutionlast eukaryotic common ancestormass spectrometryprotein interactionsproteomicsrenal failure

Identifiers

PMID42202782
PMCPMC13261697

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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.