More Like this

1. HP1 proteins compact DNA into mechanically and positionally stable phase separated domains

   https://doi.org/10.7554/eLife.64563  

   Keenen, Madeline M; Brown, David; Brennan, Lucy D; Renger, Roman; Khoo, Harrison; Carlson, Christopher R; Huang, Bo; Grill, Stephan W; Narlikar, Geeta J; Redding, Sy (March 2021, eLife)

   null (Ed.)

   In mammals, HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here, we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1β. Finally, we find that differences in each HP1 paralog’s DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale. 

   more » « less
2. Recovery from hybrid breakdown reveals a complex genetic architecture of mitonuclear incompatibilities

   https://doi.org/10.1111/mec.15985  

   Pereira, Ricardo J.; Lima, Thiago G.; Pierce‐Ward, N. Tessa; Chao, Lin; Burton, Ronald S. (June 2021, Molecular Ecology)

   Abstract Reproductive isolation is often achieved when genes that are neutral or beneficial in their genomic background become functionally incompatible in a foreign genomic background, causing inviability, sterility or other forms of low fitness in hybrids. Recent studies suggest that mitonuclear interactions are among the initial incompatibilities to evolve at early stages of population divergence across taxa. Yet, the genomic architecture of mitonuclear incompatibilities has rarely been elucidated. We employ an experimental evolution approach starting with low‐fitness F₂interpopulation hybrids of the copepodTigriopus californicus, in which frequencies of compatible and incompatible nuclear alleles change in response to an alternative mitochondrial background. After about nine generations, we observe a generalized increase in population size and in survivorship, suggesting efficiency of selection against maladaptive phenotypes. Whole genome sequencing of evolved populations showed some consistent allele frequency changes across three replicates of each reciprocal cross, but markedly different patterns between mitochondrial backgrounds. In only a few regions (~6.5% of the genome), the same parental allele was overrepresented irrespective of the mitochondrial background. About 33% of the genome showed allele frequency changes consistent with divergent selection, with the location of these genomic regions strongly differing between mitochondrial backgrounds. In 87% and 89% of these genomic regions, the dominant nuclear allele matched the associated mitochondrial background, consistent with mitonuclear co‐adaptation. These results suggest that mitonuclear incompatibilities have a complex polygenic architecture that differs between populations, potentially generating genome‐wide barriers to gene flow between closely related taxa. 

   more » « less
3. 3D genomics across the tree of life reveals condensin II as a determinant of architecture type

   https://doi.org/10.1126/science.abe2218  

   Hoencamp, Claire; Dudchenko, Olga; Elbatsh, Ahmed M. O.; Brahmachari, Sumitabha; Raaijmakers, Jonne A.; van Schaik, Tom; Sedeño Cacciatore, Ángela; Contessoto, Vinícius G.; van Heesbeen, Roy G. H. P.; van den Broek, Bram; et al (May 2021, Science)

   We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes. 

   more » « less
4. Pattern formation in acoustically levitated particle systems with competing near-field interactions

   https://doi.org/10.1103/PhysRevResearch.7.023017  

   Wu, Brady; Esposito, Edward P; Mao, Qinghao; Jaeger, Heinrich M (April 2025, Physical Review Research)

   Acoustic levitation in air provides a containerless, gravity-free platform for investigating driven many-particle systems with nonconservative interactions and underdamped dynamics. In prior work the interactions among levitated particles were limited to attractive forces from scattered sound and repulsion from hydrodynamic microstreaming. We report on experiments in which contact cohesion provides a third type of interaction. When particle size and separation are both much smaller than the sound wavelength, this interplay of three interactions results in forces that are attractive over several particle diameters, become repulsive at close approach, and are again attractive at contact. In the presence of sound-induced athermal fluctuations that generate particle collisions, the interplay of these three forces enables the formation of particle chains with anisotropic interactions that depend on chain size and shape due to multibody effects. With the control of the kinetic pathways and the strength of the contact cohesion, different patterns can be assembled, from triangular lattices to labyrinthine patterns of chains to lacelike networks of interconnected rings. These results shed light on the multibody character of acoustic interactions and can be utilized to direct the self-assembly of particles. Published by the American Physical Society2025 

   more » « less
5. From Disorder to Icosahedral Symmetry: How Conformation-Switching Subunits Enable RNA Virus Assembly

   Li, S; Tresset, G; Zandi, R (August 2025, Science advances)

   Icosahedral capsids are ubiquitous among spherical viruses, yet their assem- bly pathways and governing interactions remain elusive. We present a molecular dynamics model that incorporates essential physical and biological interactions, including protein diffusion, genome flexibility, and a conformational switch that mimics allostery and activates the elastic properties of proteins upon binding. This switch makes the simulations computationally feasible and enables the assembly of icosahedral capsids around a flexible genome—overcoming long-standing lim- itations in previous models. Using this framework, we successfully reproduce the self-assembly of subunits around a flexible genome into icosahedral shells with numbers greater than one – most notably 3, the most common structure in na- ture – a feat that rigid-body models have so far failed to achieve. We systematically explore the range of morphologies formed with different genome architectures, in line with in vitro experiments using cowpea chlorotic mottle virus capsid proteins: viral RNAs with more complex structure form more complete and stable capsids than linear ones. These results provide a predictive framework for genome-guided assembly and capsid design. 

   more » « less