Evidence map›Paper›PMID 30298815›Full record

ArticleeLife2018

Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development.

Qinwen Liu, Pinar Onal, Rhea R Datta, Julia M Rogers, Urs Schmidt-Ott, Martha L Bulyk, Stephen Small, Joseph W Thornton

Open access · goldAbstract read
In one paragraph

Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

23 citing papers in PubMed, 38 citations in OpenAlex.

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  6. Breaking anterior-posterior symmetry in the moth flybioRxiv : the preprint server for biology · 2025
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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 4 institutions in 1 country.

Qinwen Liu *Department of Ecology and Evolution, University of Chicago, Chicago, United States.
Pinar Onal *Department of Biology, New York University, New York, United States.
Rhea R Datta *Department of Biology, New York University, New York, United States.
Julia M RogersCommittee on Higher Degrees in Biophysics, Harvard University, Cambridge, United States.
Urs Schmidt-OttDepartment of Organismal Biology and Anatomy, University of Chicago, Chicago, United States.ORCID 0000-0002-1351-9472
Martha L BulykCommittee on Higher Degrees in Biophysics, Harvard University, Cambridge, United States.
Stephen SmallDepartment of Biology, New York University, New York, United States.
Joseph W ThorntonDepartment of Ecology and Evolution, University of Chicago, Chicago, United States.ORCID 0000-0001-9589-6994
University of Chicago · USBrigham and Women's Hospital · USNew York University · USHamilton College · US

Funding

ENHANCER-MEDIATED MECHANISMS OF PATTERN FORMATIONR01GM051946 · NIGMS · NEW YORK UNIVERSITY · PI SMALL, STEPHEN J · 1996 to 2019
$5.5M
High-Throughput Identification of Tissue/Cell-Type-Specific Cis Regulatory ModuleR01HG005287 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI BULYK, MARTHA L · 2010 to 2016
$3.4M
Mechanisms for the evolution of novel DNA specificity in a transcription factor fR01GM104397 · NIGMS · UNIVERSITY OF CHICAGO · PI THORNTON, JOSEPH W · 2013 to 2016
$1.3M
Deep characterization of the sequence space and evolutionary trajectories of reconstructed ancestral proteins - Resubmission 01R01GM121931 · NIGMS · UNIVERSITY OF CHICAGO · PI THORNTON, JOSEPH W · 2017 to 2020
$1.3M
Genesis and Molecular Evolution of a Master Patterning DeterminantF32GM112351 · NIGMS · UNIVERSITY OF CHICAGO · PI LIU, QINWEN · 2014 to 2014
$47k
NHGRI NIH HHS R01 HG005287NIGMS NIH HHS F32 GM112351NIGMS NIH HHS R01 GM051946NIGMS NIH HHS R01 GM104397NIGMS NIH HHS R01 GM121931NIH HHS F32GM112351NIH HHS IOS1355057NIH HHS NSF IOS0744966NIH HHS R01GM051946NIH HHS R01GM104397NIH HHS R01GM121931NIH HHS R01-HG005287
6 · The paper itself

Abstract

The ancient mechanisms that caused developmental gene regulatory networks to diversify among distantly related taxa are not well understood. Here we use ancestral protein reconstruction, biochemical experiments, and developmental assays of transgenic animals carrying reconstructed ancestral genes to investigate how the transcription factor Bicoid (Bcd) evolved its central role in anterior-posterior patterning in flies. We show that most of Bcd's derived functions are attributable to evolutionary changes within its homeodomain (HD) during a phylogenetic interval >140 million years ago. A single substitution from this period (Q50K) accounts almost entirely for the evolution of Bcd's derived DNA specificity in vitro. In transgenic embryos expressing the reconstructed ancestral HD, however, Q50K confers activation of only a few of Bcd's transcriptional targets and yields a very partial rescue of anterior development. Adding a second historical substitution (M54R) confers regulation of additional Bcd targets and further rescues anterior development. These results indicate that two epistatically interacting mutations played a major role in the evolution of Bcd's controlling regulatory role in early development. They also show how ancestral sequence reconstruction can be combined with in vivo characterization of transgenic animals to illuminate the historical mechanisms of developmental evolution.

Indexed as

Evolution, MolecularAnimalsAnimals, Genetically ModifiedBody PatterningDrosophila melanogasterDrosophila ProteinsGene Expression Regulation, DevelopmentalGene Regulatory NetworksHomeodomain ProteinsMutationPhylogenyTrans-Activatorsbcd protein, DrosophilaDrosophila ProteinsHomeodomain ProteinsTrans-Activatorsancestral reconstructionD. melanogasterevolution of developmentgeneticsgenomicshomeodomain proteins

Identifiers

PMID30298815
PMCPMC6177261
OpenAlexW2897161336

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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.