1. Physics of Living Systems

Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila

  1. Myron Barber Child VI
  2. Jack R Bateman  Is a corresponding author
  3. Amir Jahangiri
  4. Armando Reimer
  5. Nicholas C Lammers
  6. Nica Sabouni
  7. Diego Villamarin
  8. Grace C McKenzie-Smith
  9. Justine E Johnson
  10. Daniel Jost  Is a corresponding author
  11. Hernan G Garcia  Is a corresponding author
  1. University of California at Berkeley, United States
  2. Bowdoin College, United States
  3. Grenoble Alpes University, France
  4. University of California, Berkeley, United States
  5. ENS de Lyon, France
https://doi.org/10.7554/eLife.64412
Share this article
Cite this article
  1. Myron Barber Child VI
  2. Jack R Bateman
  3. Amir Jahangiri
  4. Armando Reimer
  5. Nicholas C Lammers
  6. Nica Sabouni
  7. Diego Villamarin
  8. Grace C McKenzie-Smith
  9. Justine E Johnson
  10. Daniel Jost
  11. Hernan G Garcia
(2021)
Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila
eLife 10:e64412.
https://doi.org/10.7554/eLife.64412
  2. Download BibTeX
  3. Download .RIS

Abstract

3D eukaryotic genome organization provides the structural basis for gene regulation. In Drosophila melanogaster, genome folding is characterized by somatic homolog pairing, where homologous chromosomes are intimately paired from end to end; however, how homologs identify one another and pair has remained mysterious. Recently, this process has been proposed to be driven by specifically interacting 'buttons' encoded along chromosomes. Here, we turned this hypothesis into a quantitative biophysical model to demonstrate that a button-based mechanism can lead to chromosome-wide pairing. We tested our model using live-imaging measurements of chromosomal loci tagged with the MS2 and PP7 nascent RNA labeling systems. We show solid agreement between model predictions and experiments in the pairing dynamics of individual homologous loci. Our results strongly support a button-based mechanism of somatic homolog pairing in Drosophila and provide a theoretical framework for revealing the molecular identity and regulation of buttons.

Data availability

Modeling code is available at: https://github.com/physical-biology-of-chromatin/Homologous_pairingCustom Matlab 2019b image analysis scripts can be found at https://github.com/GarciaLab/mRNADynamics/.Raw figure files of relevant plots are available at: https://www.dropbox.com/sh/cwe1t3u5q4v3yos/AACTXXBF6WiOuLuozX0MZRkba?dl=0Samples of generated data used in this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Myron Barber Child VI

    Molecular and Cell Biology, University of California at Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8563-0842

  2. Jack R Bateman

    Biology, Bowdoin College, Brunswick, United States
    For correspondence
    jbateman@bowdoin.edu
    Competing interests
    The authors declare that no competing interests exist.

  3. Amir Jahangiri

    TIMC-IMAG, Grenoble Alpes University, La Tronche, France
    Competing interests
    The authors declare that no competing interests exist.

  4. Armando Reimer

    Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Nicholas C Lammers

    Biophysics Graduate Group, University of California, Berkeley, Oakland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6832-6152

  6. Nica Sabouni

    Molecular and Cell Biology, University of California at Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Diego Villamarin

    Biology, Bowdoin College, Brunswick, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3265-1740

  8. Grace C McKenzie-Smith

    Biology, Bowdoin College, Brunswick, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Justine E Johnson

    Biology, Bowdoin College, Brunswick, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Daniel Jost

    Laboratory of Biology and Modelling of the Cell, ENS de Lyon, Lyon, France
    For correspondence
    daniel.jost@ens-lyon.fr
    Competing interests
    The authors declare that no competing interests exist.

  11. Hernan G Garcia

    Molecular and Cell Biology, Physics, University of California, Berkeley, Berkeley, United States
    For correspondence
    hggarcia@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5212-3649

Funding

Burroughs Wellcome Fund (Career Award at the Scientific Interface)

  • Hernan G Garcia

ITMO Cancer (BIO2015-08)

  • Daniel Jost

National Institutes of Health (P20 GM0103423,R15 GM132896-01)

  • Jack R Bateman

National Science Foundation (CAREER Award 1349779)

  • Jack R Bateman

Alfred P. Sloan Foundation (Sloan Research Fellowship)

  • Hernan G Garcia

Human Frontier Science Program

  • Hernan G Garcia

Searle Scholars Program

  • Hernan G Garcia

Shurl and Kay Curci Foundation

  • Hernan G Garcia

Hellman Foundation

  • Hernan G Garcia

National Institutes of Health (Director's New Innovator Award,DP2 OD024541-01)

  • Hernan G Garcia

National Science Foundation (CAREER Award,1652236)

  • Hernan G Garcia

Agence Nationale pour la Recherche (ANR-18-CE12-0006-03,ANR-18-CE45-0022-01)

  • Daniel Jost

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2021, Child et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,552
    views
  • 194
    downloads
  • 22
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Myron Barber Child VI
  2. Jack R Bateman
  3. Amir Jahangiri
  4. Armando Reimer
  5. Nicholas C Lammers
  6. Nica Sabouni
  7. Diego Villamarin
  8. Grace C McKenzie-Smith
  9. Justine E Johnson
  10. Daniel Jost
  11. Hernan G Garcia
(2021)
Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila
eLife 10:e64412.
https://doi.org/10.7554/eLife.64412

Share this article

https://doi.org/10.7554/eLife.64412

Categories and tags

Research organism

Further reading

    1. Computational and Systems Biology
    2. Physics of Living Systems

    Emergence of planar cell polarity from the interplay of local interactions and global gradients

    Divyoj Singh, Sriram Ramaswamy ... Mohd Suhail Rizvi
    Research Article Updated

    Planar cell polarity (PCP) – tissue-scale alignment of the direction of asymmetric localization of proteins at the cell-cell interface – is essential for embryonic development and physiological functions. Abnormalities in PCP can result in developmental imperfections, including neural tube closure defects and misaligned hair follicles. Decoding the mechanisms responsible for PCP establishment and maintenance remains a fundamental open question. While the roles of various molecules – broadly classified into ‘global’ and ‘local’ modules – have been well-studied, their necessity and sufficiency in explaining PCP and connecting their perturbations to experimentally observed patterns have not been examined. Here, we develop a minimal model that captures the proposed features of PCP establishment – a global tissue-level gradient and local asymmetric distribution of protein complexes. The proposed model suggests that while polarity can emerge without a gradient, the gradient not only acts as a global cue but also increases the robustness of PCP against stochastic perturbations. We also recapitulated and quantified the experimentally observed features of swirling patterns and domineering non-autonomy, using only three free model parameters - rate of protein binding to membrane, the concentration of PCP proteins, and the gradient steepness. We explain how self-stabilizing asymmetric protein localizations in the presence of tissue-level gradient can lead to robust PCP patterns and reveal minimal design principles for a polarized system.

    1. Physics of Living Systems

    A scale-invariant log-normal droplet size distribution below the critical concentration for protein phase separation

    Tommaso Amico, Samuel Toluwanimi Dada ... Amos Maritan
    Research Article

    Many proteins have been recently shown to undergo a process of phase separation that leads to the formation of biomolecular condensates. Intriguingly, it has been observed that some of these proteins form dense droplets of sizeable dimensions already below the critical concentration, which is the concentration at which phase separation occurs. To understand this phenomenon, which is not readily compatible with classical nucleation theory, we investigated the properties of the droplet size distributions as a function of protein concentration. We found that these distributions can be described by a scale-invariant log-normal function with an average that increases progressively as the concentration approaches the critical concentration from below. The results of this scaling analysis suggest the existence of a universal behaviour independent of the sequences and structures of the proteins undergoing phase separation. While we refrain from proposing a theoretical model here, we suggest that any model of protein phase separation should predict the scaling exponents that we reported here from the fitting of experimental measurements of droplet size distributions. Furthermore, based on these observations, we show that it is possible to use the scale invariance to estimate the critical concentration for protein phase separation.

    1. Computational and Systems Biology
    2. Physics of Living Systems

    Intraspecific predator interference promotes biodiversity in ecosystems

    Ju Kang, Shijie Zhang ... Xin Wang
    Research Article

    Explaining biodiversity is a fundamental issue in ecology. A long-standing puzzle lies in the paradox of the plankton: many species of plankton feeding on a limited variety of resources coexist, apparently flouting the competitive exclusion principle (CEP), which holds that the number of predator (consumer) species cannot exceed that of the resources at a steady state. Here, we present a mechanistic model and demonstrate that intraspecific interference among the consumers enables a plethora of consumer species to coexist at constant population densities with only one or a handful of resource species. This facilitated biodiversity is resistant to stochasticity, either with the stochastic simulation algorithm or individual-based modeling. Our model naturally explains the classical experiments that invalidate the CEP, quantitatively illustrates the universal S-shaped pattern of the rank-abundance curves across a wide range of ecological communities, and can be broadly used to resolve the mystery of biodiversity in many natural ecosystems.