Evidence map›Paper›PMID 27075724›Full record

ArticleGenetics2016

Functional Divergence of the Nuclear Receptor NR2C1 as a Modulator of Pluripotentiality During Hominid Evolution.

Jennifer L Baker, Katherine A Dunn, Joseph Mingrone, Bernard A Wood, Beverly A Karpinski, Chet C Sherwood, Derek E Wildman, Thomas M Maynard, Joseph P Bielawski

Open access · bronzeAbstract read
In one paragraph

Article in Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
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

12 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Convergent patterns of evolution of mitochondrial oxidative phosphorylation (OXPHOS) genes in electric fishes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020
    Article
  8. Article
  9. Article
  10. The EMBO journal · 2018
    Article
  11. Article
  12. 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

9 authors at 4 institutions in 2 countries.

Jennifer L BakerCenter for the Advanced Study of Human Paleobiology, George Washington University, Washington, DC 20052 George Washington Institute for Neuroscience, George Washington University, Washington, DC 20052 Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 JenniferLBaker7@gmail.com J.Bielawski@dal.ca.ORCID 0000-0002-5192-2377
Katherine A DunnDepartment of Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
Joseph MingroneDepartment of Mathematics and Statistics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
Bernard A WoodCenter for the Advanced Study of Human Paleobiology, George Washington University, Washington, DC 20052 Human Origins Program, National Museum of Natural History, Smithsonian Institution, Washington, DC 20560.
Beverly A KarpinskiDepartment of Anatomy and Regenerative Biology, George Washington University, Washington, DC 20052.
Chet C SherwoodCenter for the Advanced Study of Human Paleobiology, George Washington University, Washington, DC 20052 George Washington Institute for Neuroscience, George Washington University, Washington, DC 20052.
Derek E WildmanDepartment of Molecular and Integrative Physiology, University of Illinois Urbana-Champaign, Champaign, Illinois 61801 Institute for Genomic Biology, University of Illinois Urbana-Champaign, Champaign, Illinois 61801.
Thomas M MaynardGeorge Washington Institute for Neuroscience, George Washington University, Washington, DC 20052 Department of Pharmacology and Physiology, George Washington University, Washington, DC 20052.
Joseph P BielawskiDepartment of Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2 Department of Mathematics and Statistics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2 JenniferLBaker7@gmail.com J.Bielawski@dal.ca.
George Washington University · USDalhousie University · CANational Museum of Natural History · USUniversity of Illinois Urbana-Champaign · US

Funding

CIHR CMF-108026
6 · The paper itself

Abstract

Genes encoding nuclear receptors (NRs) are attractive as candidates for investigating the evolution of gene regulation because they (1) have a direct effect on gene expression and (2) modulate many cellular processes that underlie development. We employed a three-phase investigation linking NR molecular evolution among primates with direct experimental assessment of NR function. Phase 1 was an analysis of NR domain evolution and the results were used to guide the design of phase 2, a codon-model-based survey for alterations of natural selection within the hominids. By using a series of reliability and robustness analyses we selected a single gene, NR2C1, as the best candidate for experimental assessment. We carried out assays to determine whether changes between the ancestral and extant NR2C1s could have impacted stem cell pluripotency (phase 3). We evaluated human, chimpanzee, and ancestral NR2C1 for transcriptional modulation of Oct4 and Nanog (key regulators of pluripotency and cell lineage commitment), promoter activity for Pepck (a proxy for differentiation in numerous cell types), and average size of embryological stem cell colonies (a proxy for the self-renewal capacity of pluripotent cells). Results supported the signal for alteration of natural selection identified in phase 2. We suggest that adaptive evolution of gene regulation has impacted several aspects of pluripotentiality within primates. Our study illustrates that the combination of targeted evolutionary surveys and experimental analysis is an effective strategy for investigating the evolution of gene regulation with respect to developmental phenotypes.

Indexed as

Evolution, MolecularAnimalsCell DifferentiationCell LineConserved SequenceHominidaeHumansMiceNanog Homeobox ProteinNuclear Receptor Subfamily 2, Group C, Member 1Octamer Transcription Factor-3Phosphoenolpyruvate Carboxykinase (ATP)Pluripotent Stem CellsProtein DomainsNanog Homeobox ProteinNuclear Receptor Subfamily 2, Group C, Member 1Octamer Transcription Factor-3Phosphoenolpyruvate Carboxykinase (ATP)ancestral gene reconstruction (AGR)codon modelshominid evolutionary surveyNR2C1nuclear receptorspluripotentialitytesticular receptor 2 (TR2)

Identifiers

PMID27075724
PMCPMC4896202
OpenAlexW2340373989

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.