Evidence map›Paper›PMID 34433829›Full record

ArticleNature communications2021

Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans.

PingHsun Hsieh, Vy Dang, Mitchell R Vollger, Yafei Mao, Tzu-Hsueh Huang, Philip C Dishuck, Carl Baker, Stuart Cantsilieris, Alexandra P Lewis, Katherine M Munson and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  5. Article
  6. TCAF1 promotes TRPV2-mediated CaNature communications · 2024
    Article
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  8. Review
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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

14 authors at 3 institutions in 2 countries.

PingHsun HsiehDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA. hsiehph@uw.edu.ORCID 0000-0001-8294-6227
Vy DangDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Mitchell R VollgerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0002-8651-1615
Yafei MaoDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0002-9648-4278
Tzu-Hsueh HuangDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Philip C DishuckDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0003-2223-9787
Carl BakerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Stuart CantsilierisDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Alexandra P LewisDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Katherine M MunsonDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0001-8413-6498
Melanie SorensenDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
AnneMarie E WelchDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Jason G UnderwoodDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Evan E EichlerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA. eee@gs.washington.edu.ORCID 0000-0002-8246-4014
University of Washington · USHoward Hughes Medical Institute · USWalter and Eliza Hall Institute of Medical Research · AU

Funding

Sequence and Assembly of Segmental DuplicationsR01HG002385 · NHGRI · UNIVERSITY OF WASHINGTON · PI Evan Eichler · 2001 to 2026
$13.3M
The fitness effects of de novo structural variantsK99HG011041 · NHGRI · UNIVERSITY OF WASHINGTON · PI HSIEH, PINGHSUN · 2020 to 2021
$264k
Howard Hughes Medical InstituteNHGRI NIH HHS K99 HG011041NHGRI NIH HHS R01 HG002385
6 · The paper itself

Abstract

TRP channel-associated factor 1/2 (TCAF1/TCAF2) proteins antagonistically regulate the cold-sensor protein TRPM8 in multiple human tissues. Understanding their significance has been complicated given the locus spans a gap-ridden region with complex segmental duplications in GRCh38. Using long-read sequencing, we sequence-resolve the locus, annotate full-length TCAF models in primate genomes, and show substantial human-specific TCAF copy number variation. We identify two human super haplogroups, H4 and H5, and establish that TCAF duplications originated ~1.7 million years ago but diversified only in Homo sapiens by recurrent structural mutations. Conversely, in all archaic-hominin samples the fixation for a specific H4 haplotype without duplication is likely due to positive selection. Here, our results of TCAF copy number expansion, selection signals in hominins, and differential TCAF2 expression between haplogroups and high TCAF2 and TRPM8 expression in liver and prostate in modern-day humans imply TCAF diversification among hominins potentially in response to cold or dietary adaptations.

Indexed as

Gene DuplicationSelection, GeneticAnimalsDNA Copy Number VariationsEvolution, MolecularGenome, HumanHaplotypesHominidaeHumansMembrane ProteinsNeanderthalsPhylogenyMembrane ProteinsTCAF2 protein, humanTRPM8 channel-associated factor 1 protein, human

Identifiers

PMID34433829
PMCPMC8387397
OpenAlexW3193581299

What OpenQuestion holds

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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.