Evidence map›Paper›PMID 41066569›Full record

ArticleScience (New York, N.Y.)2025

A genome-to-proteome map reveals how natural variants drive proteome diversity and shape fitness.

Christopher M Jakobson, Johannes Hartl, Pauline Trébulle, Michael Mülleder, Daniel F Jarosz, Markus Ralser

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Proteoforms as the true units of physiological function.European journal of applied physiology · 2026
    Review
  6. Article
  7. Protein structure shapes natural genetic variation andbioRxiv : the preprint server for biology · 2025
    Article
  8. 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

6 authors.

Christopher M Jakobson *Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-7594-7416
Johannes Hartl *Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0001-8470-5355
Pauline TrébulleCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0002-4729-5032
Michael MüllederCore Facility High-Throughput Mass Spectrometry, Charité - Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0001-9792-3861
Daniel F Jarosz *Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-3497-5888
Markus Ralser *Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0001-9535-7413

Funding

Brain-wide screen for a neural pacemaker of agingR01AG063418 · NIA · STANFORD UNIVERSITY · PI BRUNET, ANNE, DEISSEROTH, KARL A. · 2018 to 2022
$13.5M
Discovery of protein aggregates during vertebrate aging and neurodegenerationRF1AG057334 · NIA · STANFORD UNIVERSITY · PI BRUNET, ANNE, JAROSZ, DANIEL · 2017 to 2017
$3.7M
Protein-based Molecular Memories in Gene Regulation, Disease, and DevelopmentDP2GM119140 · NIGMS · STANFORD UNIVERSITY · PI JAROSZ, DANIEL · 2015 to 2015
$2.4M
Mechanisms of Action of Natural Genetic VariationR01HG012366 · NHGRI · STANFORD UNIVERSITY · PI Daniel Jarosz · 2023 to 2026
$1.5M
Using self-templating proteins to spatiotemporally organize biochemistryF32GM125162 · NIGMS · STANFORD UNIVERSITY · PI JAKOBSON, CHRISTOPHER MATTHEW · 2017 to 2019
$179k
NHGRI NIH HHS R01 HG012366NIA NIH HHS R01 AG063418NIA NIH HHS RF1 AG057334NIGMS NIH HHS DP2 GM119140NIGMS NIH HHS F32 GM125162
6 · The paper itself

Abstract

Understanding how genetic variation translates into complex phenotypes remains a fundamental challenge. In this work, we address this by mapping genome-to-proteome relationships in 800 progeny of a cross between two yeast strains adapted to distinct environments. Despite the modest genetic distance between the parents, we observed notable proteomic diversity and mapped more than 6400 genotype-protein associations, with more than 1600 linked to individual genetic variants. Proteomic adaptation emerged from a conserved network of cis- and trans-regulatory variants, often originating from proteins not traditionally linked to gene regulation. This atlas allowed us to forecast organismal fitness effects across diverse conditions. By connecting genomic and proteomic landscapes at unprecedented resolution, our study provides a framework for predicting the phenotypic outcomes of natural genetic variation.

Indexed as

Genetic FitnessGenetic VariationGenome, FungalProteomeSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsAdaptation, PhysiologicalPhenotypeProteomeSaccharomyces cerevisiae Proteins

Identifiers

PMID41066569
PMCPMC12989164

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Registered trials

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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.