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Differential pleiotropy and HOX functional organization.

Lovesha Sivanantharajah1, Anthony Percival-Smith1

  • 1Department of Biology, The University of Western Ontario, BGS231, London, Ontario, Canada N6A 5B7.

Developmental Biology
|December 3, 2014
PubMed
Summary
This summary is machine-generated.

Transcription factors (TFs) may not be strictly modular. Homeotic selector (HOX) proteins show differential pleiotropy, where conserved motifs contribute additively, suggesting greater evolutionary impact of sequence changes.

Keywords:
Differential pleiotropyEnsemble mediated allosteryEvolution and developmentFunctional domain structureHOXSLiMsTranscription factors

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Evolutionary Biology

Background:

  • The traditional view posits transcription factors (TFs) are modular, built from separable domains with distinct functions.
  • This modular model, exemplified by GAL4, may not represent the norm for all TFs.
  • Recent research challenges this archetypal view, particularly for Homeotic selector (HOX) proteins.

Purpose of the Study:

  • To investigate the functional organization of HOX proteins.
  • To explore the concept of differential pleiotropy in HOX protein function.
  • To reassess the archetypal model of TF organization based on new findings.

Main Methods:

  • Analysis of HOX protein motifs and domains.
  • Investigation of differential pleiotropy and its contribution to HOX activity.
  • Consideration of short linear motifs (SLiMs) in HOX protein evolution.

Main Results:

  • HOX proteins exhibit differential pleiotropy, with conserved motifs making small, additive, tissue-specific contributions.
  • Many of these motifs are identified as short linear motifs (SLiMs), suggesting sequence plasticity.
  • This implies protein sequence changes in HOX TFs could significantly impact morphological diversity.

Conclusions:

  • The modular view of TFs may be an oversimplification, with HOX proteins demonstrating a more nuanced functional architecture.
  • Differential pleiotropy, linked to SLiMs, suggests a greater role for sequence variation in HOX-mediated evolution.
  • HOX protein function may arise from an ensemble of allosteric states, integrating diverse developmental signals.