Evidence map›Paper›PMID 27984726›Full record

ArticleCell2016

Functional Segregation of Overlapping Genes in HIV.

Jason D Fernandes, Tyler B Faust, Nicolas B Strauli, Cynthia Smith, David C Crosby, Robert L Nakamura, Ryan D Hernandez, Alan D Frankel

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. A CRISPR-Cas Cure for HIV/AIDS.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. 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

8 authors at 1 institution in 1 country.

Jason D FernandesDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA; Program in Pharmaceutical Sciences and Pharmacogenomics, University of California San Francisco, San Francisco, CA 94158, USA.
Tyler B FaustDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA; Tetrad Program, Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
Nicolas B StrauliDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA 94158, USA.
Cynthia SmithDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
David C CrosbyDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
Robert L NakamuraDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
Ryan D HernandezDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA.
Alan D FrankelDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: frankel@cgl.ucsf.edu.
University of California, San Francisco · US

Funding

X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRANKEL, ALAN D · 2007 to 2018
$48.8M
PREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
Microbial Pathogenesis and Host DefenseT32AI060537 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joanne N. Engel · 2004 to 2026
$6.5M
NIAID NIH HHS T32 AI060537NICHD NIH HHS T32 HD007470NIGMS NIH HHS P50 GM082250NIGMS NIH HHS T32 GM007175
6 · The paper itself

Abstract

Overlapping genes pose an evolutionary dilemma as one DNA sequence evolves under the selection pressures of multiple proteins. Here, we perform systematic statistical and mutational analyses of the overlapping HIV-1 genes tat and rev and engineer exhaustive libraries of non-overlapped viruses to perform deep mutational scanning of each gene independently. We find a "segregated" organization in which overlapped sites encode functional residues of one gene or the other, but never both. Furthermore, this organization eliminates unfit genotypes, providing a fitness advantage to the population. Our comprehensive analysis reveals the extraordinary manner in which HIV minimizes the constraint of overlapping genes and repurposes that constraint to its own advantage. Thus, overlaps are not just consequences of evolutionary constraints, but rather can provide population fitness advantages.

Indexed as

Biological EvolutionEntropyGenetic FitnessHIV-1HIV InfectionsHumansMutationOpen Reading Framesrev Gene Products, Human Immunodeficiency Virustat Gene Products, Human Immunodeficiency Virusrev Gene Products, Human Immunodeficiency Virusrev protein, Human Immunodeficiency Virus-1tat Gene Products, Human Immunodeficiency Virusalanine scanningdeep mutational scanningevolutionHIVoverlapping reading framesoverprintingRevTatviral evolutionvirus

Identifiers

PMID27984726
PMCPMC5287106
OpenAlexW2562684256

What OpenQuestion holds

Textmetadata
LicenceTDM
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.