Biology subjects

Seim, I.

Publications and source records attributed to Seim, I..

At least 19 recordsLinked to original sources

bioRxiv2026

Eleven deep-sea coral genome assemblies unveil insights into evolution, adaptation, and coral biodiversity

Deep-sea corals are vital in maintaining coral ecosystem biodiversity, yet their genetic characteristics remain largely unexplored. Here, we present 11 deep-sea coral genome assemblies, including four Hexacorallia and seven Octocorallia species, significantly contributing new genomic information across two orders. Our analysis reveals the historical dynamics of coral speciation and the influence of environmental factors on the evolution of coral reef ecosystems.Total of 126 horizontal gene transfer (HGT) events were detected, among which genes from the ancestor of symbiodiniaceae indicate that the ancestors of deep-sea corals may have inhabited shallow-sea environments. Notably, several of these HGTs are involved in phosphorus (PhnX/PhnW) and cholesterol (DHCR7) metabolisms within corals, indicating that HGTs may serve as an adaptive survival strategy for the coral holobionts. Deep-sea corals also rely on symbiotic bacteria to synthesize 10 essential amino acids (such as valine and tyrosine), retaining only partial amino acid synthesis capacity. In addition, we investigated the evolution of key biological rhythm genes and temperature adaptation in corals. The loss of key rhythm genes (e.g., clock and cry) in deep-sea corals and copy number difference of genes related to heat stress (e.g., Cbl-b and Rchy) revealed genetic difference between deep-sea and shallow-sea corals. Our new genome assemblies enhance the understanding of deep-sea coral evolution, biodiversity, and adaptation, providing a genetic foundation for coral conservation.

genomics↗

bioRxiv2026

The genetic repertoire of the deep sea: from sequence to structure and function

The deep sea as the largest and maybe most hostile environment on Earth is still underexplored especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures, and used it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity, yet substantial structural conservation of proteins. Especially proteins involved in replication, recombination, and repair were identified to be under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as a unique evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.

bioinformatics↗

bioRxiv2025

mRNA interactions promote cotranslational association of heteromeric membrane proteins

Heteromeric membrane proteins play crucial physiological roles, yet how they are formed remains poorly understood. Heteromeric hERG1a/1b ion channels, essential for maintaining normal cardiac rhythm, assemble via cotranslational association of their encoding mRNAs. We hypothesized that direct hERG1a and 1b mRNA interactions facilitate this process. Using fluorescence colocalization and free energy of binding predictions, we found that hERG1a and 1b mRNAs form specific heterotypic condensates in vitro, suggesting direct interactions. When hERG1a mRNA was altered by synonymous mutations predicted to reduce its structural diversity and ability to interact with other mRNAs, overlap with hERG1b was dramatically diminished both in vitro and in cells, indicating weakened interactions. Reducing hERG1a structural diversity also influenced its translational complexes, defined by overlapping between fluorescently labeled mRNA and encoded protein (centroids within 400 nm). Whereas most of the wild-type hERG1a mRNA translates within heterotypic complexes, likely reflecting the biogenesis of hERG1a/1b heteromeric assemblies, reducing hERG1a structural diversity yielded more homotypic translational condensates and fewer hERG1a/1b heterotypic ones. This result suggests that the strength of mRNA interactions impact ion channel biogenesis. Further analysis of the heterotypic translational complexes revealed two distinct classes: a) simultaneous translation of both subunits and b) sequential association of fully translated hERG1b with translating hERG1a. Notably, reducing hERG1a structural diversity and interactions with 1b shifted translation toward the sequential mode. These findings identify a new role of mRNA sequence, structure, and interactions in orchestrating the cotranslational association of important heteromeric membrane proteins. SIGNIFICANCEThe physiological diversity of membrane protein complexes arises in part from the mixing of related yet functionally distinct subunits such as those forming "heteromeric" ion channels. How this mixing is achieved is not well understood. Here, we show that subunits composing heteromeric hERG1a/1b ion channels, crucial for normal cardiac function, predominantly associate in complexes where both subunits are simultaneously translated. This cotranslation is promoted by the association of the encoding mRNAs. Silent mutations disrupting hERG1a and 1b mRNA association, without altering the encoded protein, diminish simultaneous translation in favor of hERG1a translational complexes alone or in association with fully synthesized hERG1b. This study highlights the significant impact of RNA sequence, structure, and association on the formation of heteromeric membrane proteins.

biophysics↗

bioRxiv2025

Cooperativity in septin polymerization is tunable by ionic strength and membrane adsorption

Cells employ cytoskeletal polymers to move, divide, and pass information inside and outside of the cell. Previous work on eukaryotic cytoskeletal elements such as actin, microtubules, and intermediate filaments investigating the mechanisms of polymerization have been critical to understand how cells control the assembly of the cytoskeleton. Most biophysical analyses have considered cooperative versus isodesmic modes of polymerization; this framework is useful for specifying functions of regulatory proteins that control nucleation and understanding how cells regulate elongation in time and space. The septins are considered a fourth component of the eukaryotic cytoskeleton, but they are poorly understood in many ways despite their conserved roles in membrane dynamics, cytokinesis, and cell shape, and in their links to a myriad of human diseases. Because septin function is intimately linked to their assembled state, we set out to investigate the mechanisms by which septin polymers elongate under different conditions. We used simulations, in vitro reconstitution of purified septin complexes, and quantitative microscopy to directly interrogate septin polymerization behaviors in solution and on synthetic lipid bilayers of different geometries. We first used reactive Brownian dynamics simulations to determine if the presence of a membrane induces cooperativity to septin polymerization. We then used fluorescence correlation spectroscopy (FCS) to assess septins ability to form filaments in solution at different salt conditions. Finally, we investigated septin membrane adsorption and polymerization on planar and curved supported lipid bilayers. Septins clearly show signs of salt-dependent cooperative assembly in solution, but cooperativity is limited by binding a membrane. Thus, septin assembly is dramatically influenced by extrinsic conditions and substrate properties and can show properties of both isodesmic and cooperative polymers. This versatility in assembly modes may explain the extensive array of assembly types, functions, and subcellular locations in which septins act. SIGNIFICANCEThe septin cytoskeleton plays conserved and essential roles in cell division, membrane remodeling, and intracellular signaling with links to varied human diseases. Unlike actin and microtubules, whose polymerization dynamics have been extensively characterized, the molecular details of septin polymerization remain poorly understood. Here, we investigate the mode of septin polymerization through the lens of isodesmic and cooperative polymer assembly models in solution, on planar and curved supported membranes, and under different ionic conditions. Our findings show that the mechanisms of septin assembly are highly sensitive to ionic conditions, membrane geometry, and protein concentrations. Notably, assembly can show either cooperative or isodesmic properties depending on context, thereby revealing unexpected plasticity.

biochemistry↗

bioRxiv2025

RNA promotes synapsin coacervation and modulates local translation

Condensates at synapses organize synaptic vesicle (SV) clusters and are essential for efficient neurotransmitter release. While it is established that RNA granules traffic along the axons, the function of RNA at the presynapse remains unclear. Here, we uncover a direct structural role of coding RNAs in organizing presynaptic condensates by focusing on SV clusters, condensates between synapsin-1 and lipid vesicles, a defining feature of nerve terminals. Using in vitro reconstitution systems, we show that RNA drives synapsin-1 coacervation, with bias toward structured RNAs being more effective at promoting phase transitions. The importance of RNA was confirmed in living synapses, where acute disruption of native RNA induces a dispersion of SVs and synapsin. Conversely, ectopically expressed SV-like condensates have the ability to recruit the translational machinery. The microscopy-based in vitro translation assay demonstrates increased translation efficiency within synapsin-1/RNA condensates. Together, our work indicates a novel structural role of RNAs in modulating SV condensates.

cell biology↗

bioRxiv2024

RNA encodes physical information

Most amino acids are encoded by multiple codons, making the genetic code degenerate. Synonymous mutations affect protein translation and folding, but their impact on RNA itself is often neglected. We developed a genetic algorithm that introduces synonymous mutations to control the diversity of structures sampled by an mRNA. The behavior of the designed mRNAs reveals a physical code layered in the genetic code. We find that mRNA conformational heterogeneity directs physical properties and functional outputs of RNA-protein complexes and biomolecular condensates. The role of structure and disorder of proteins in biomolecular condensates is well appreciated, but we find that RNA conformational heterogeneity is equally important. This feature of RNA enables both evolution and engineers to build cellular structures with specific material and responsive properties.

biophysics↗

bioRxiv2023

Biomolecular condensates in fungi are tuned to function at specific temperatures

Temperature can impact every reaction and molecular interaction essential to a cell. For organisms that cannot regulate their own temperature, a major challenge is how to adapt to temperatures that fluctuate unpredictability and on variable timescales. Biomolecular condensation offers a possible mechanism for encoding temperature-responsiveness and robustness into cell biochemistry and organization. To explore this idea, we examined temperature adaptation in a filamentous-growing fungus called Ashbya gossypii that engages biomolecular condensates containing the RNA-binding protein Whi3 to regulate mitosis and morphogenesis. We collected wild isolates of Ashbya that originate in different climates and found that mitotic asynchrony and polarized growth, which are known to be controlled by the condensation of Whi3, are temperature sensitive. Sequence analysis in the wild strains revealed changes to specific domains within Whi3 known to be important in condensate formation. Using an in vitro condensate reconstitution assay we found that temperature impacts the relative abundance of protein to RNA within condensates and that this directly impacts the material properties of the droplets. Finally, we found that exchanging Whi3 genes between warm and cold isolates was sufficient to rescue some, but not all, condensate-related phenotypes. Together these data demonstrate that material properties of Whi3 condensates are temperature sensitive, that these properties are important for function, and that sequence optimizes properties for a given climate.

cell biology↗

bioRxiv2023

Sirenian genomes illuminate the evolution of fully aquatic species within the mammalian superorder Afrotheria

Sirenians of the diverse superorder Afrotheria were the first mammals to retransition from land to water and are the sole herbivorous marine mammals, but little is known about the underlying genomic changes. Here, we generated a chromosome-level dugong (Dugong dugon) genome. A comparison of our assembly and a recent West Indian manatee genome with other afrotherian genomes revealed possible molecular solutions to aquatic life by sirenians, including a shift in daily activity patterns (circadian clock) and tolerance to a high-iodine plant diet mediated through changes in the iodide transporter NIS (SLC5A5) and its co-transporters. Functional in vitro assays confirmed that sirenian amino acid substitutions alter the properties of the circadian clock protein PER2 and NIS. Sirenians show evidence of convergent regression of integumentary system (skin and its appendages) genes with cetaceans, the only other fully aquatic mammal group. Our analysis also uncovered gene losses that may be maladaptive in a modern environment, including a candidate gene (KCNK18) for sirenian cold stress syndrome likely lost during their evolutionary shift in daily activity patterns. Finally, genomes from nine Australian locations and the functionally extinct Okinawan population confirm and date a genetic break on the Australian east coast and highlight the need for whole-genome resequencing data from small or isolated dugong populations worldwide for conservation and genetic management.

evolutionary biology↗

bioRxiv2023

Evolutionary transcriptomics reveals longevity mostly driven by polygenic and indirect selection in mammals

The maximum lifespan varies more than 100-fold in mammals. This experiment of nature may uncover of the evolutionary forces and molecular features that define longevity. To understand the relationship between gene expression variation and maximum lifespan, we carried out a comparative transcriptomics analysis of liver, kidney, and brain tissues of 106 mammalian species. We found that expression is largely conserved and very limited genes exhibit common expression patterns with longevity in all the three organs analyzed. However, many pathways, e.g., "Insulin signaling pathway", and "FoxO signaling pathway", show accumulated correlations with maximum lifespan across mammals. Analyses of selection features further reveal that methionine restriction related genes whose expressions associated with longevity, are under strong selection in long-lived mammals, suggesting that a common approach could be utilized by natural selection and artificial intervention to control lifespan. These results suggest that natural lifespan regulation via gene expression is likely to be driven through polygenic model and indirect selection.

evolutionary biology↗

bioRxiv2023

Dynamical control enables the formation of demixed biomolecular condensates

Macromolecular phase separation underlies the regulated formation and dissolution of biomolecular condensates. What is unclear is how condensates of distinct and shared macromolecular compositions form and coexist within cellular milieus. Here, we use theory and computation to establish thermodynamic criteria that must be satisfied to achieve compositionally distinct condensates. We applied these criteria to an archetypal ribonucleoprotein condensate and discovered that demixing into distinct protein-RNA condensates cannot be the result of purely thermodynamic considerations. Instead, demixed, compositionally distinct condensates arise due to asynchronies in timescales that emerge from differences in long-lived protein-RNA and RNA-RNA crosslinks. This type of dynamical control is also found to be active in live cells whereby asynchronous production of molecules is required for realizing demixed protein-RNA condensates. We find that interactions that exert dynamical control provide a versatile and generalizable way to influence the compositions of coexisting condensates in live cells.

biophysics↗

bioRxiv2021

Diversity, function and evolution of aquatic vertebrate genomes

Aquatic vertebrates consist of jawed fish (cartilaginous fish and bony fish), aquatic mammals, reptiles and amphibians. Here, we present a comprehensive analysis of 630 aquatic vertebrate genomes to generate a standardized compendium of genomic data. We demonstrate its value by assessing their genome features as well as illuminating gene families related to the transition from water to land, such as Hox genes and olfactory receptor genes. We found that LINEs are the major transposable element (TE) type in cartilaginous fish and aquatic mammals, while DNA transposons are the dominate type in bony fish. To our surprise, TE types are not fixed in amphibians, the first group that transitioned to living on land. These results illustrate the value of a unified resource for comparative genomic analyses of aquatic vertebrates. Our data and strategy are likely to support all evolutionary and ecological research on vertebrates.

genomics↗

bioRxiv2021

Diversity, function and evolution of marine invertebrate genomes

Invertebrates, animals (metazoans) without backbones, encompass [~]97% of all animal yet remains understudied. They have provided insights into molecular mechanisms underlying fundamentally identical mechanisms in phylogenetically diverse animals, including vertebrates. Marine invertebrates have long fascinated researchers due to their abundance, diversity, adaptations, and impact on ecosystems and human economies. Here, we report a compendium and appraisal of 190 marine invertebrate genomes spanning 21 phyla, 43 classes, 92 orders, and 134 families. We identify a high proportion and long unit size of tandem repeats, likely contributing to reported difficulties in invertebrate genome assembly. A well-supported phylogenetic tree of marine invertebrates from 974 single-copy orthologous genes resolved topological controversies. We show that Ctenophora is at the basal phylum and Porifera is the sister group of Parahoxozoa; that Xenacoelomorpha is within Bilateria and is the sister group to Protostomia, rejecting three out of four hypotheses in the field; and that Bryozoa is at the basal position of Lophotrochozoa, not grouped into Lophophorata. We also present insights into the genetic underpinnings of metazoans from Hox genes, innate immune gene families, and nervous system gene families. Our marine invertebrate genome compendium provides a unified foundation for studies on their evolution and effects on ecological systems and human life.

genomics↗

bioRxiv2021

Diversity, function and evolution of marine microbe genomes

Trillions of marine bacterial, archaeal and viral species contribute to the majority diversity of life on Earth. In the current study, we have done a comprehensive review of all the published studies of marine microbiome by re-analyzing most of the available high throughput sequencing data. We collected 17.59 Tb sequencing data from 8,165 metagenomic and prokaryotic samples, and systematically evaluated the genome characters, including genome size, GC content, phylogeny, and the functional and ecological roles of several typical phyla. A genome catalogue of 9,070 high quality genomes and a gene catalogue including 156,209,709 genes were constructed, representing the most integrate marine prokaryotic datasets till now. The genome size of Alphaproteobacteria and Actinobacteria was significant correlated to their GC content. A total of 44,322 biosynthetic gene clusters distributed in 53 types were detected from the reconstructed marine prokaryotic genome catalogue. Phylogenetic annotation of the 8,380 bacterial and 690 archaeal species revealed that most of the known bacterial phyla (99/111), including 62 classes and 181 orders, and four extra unclassified genomes from two candidate novel phyla were detected. In addition, taxonomically unclassified species represented a substantial fraction of 64.56% and 80.29% of the phylogenetic diversity of Bacteria and Archaea respectively. The genomic and ecological features of three groups of Cyanobacteria, luminous bacteria and methane-metabolizing archaea, including inhabitant preference, geolocation distribution and others were through discussed. Our database provides a comprehensive resource for marine microbiome, which would be a valuable reference for studies of marine life origination and evolution, ecology monitor and protection, bioactive compound development.

microbiology↗

bioRxiv2021

Draft genomes of a male and female Australian jacky dragon (Amphibolurus muricatus)

Australia is remarkable for its lizard diversity, with very high endemicity because of continental-scale diversification and adaptive radiation during prolonged isolation. We here employed stLFR linked-read technology to generate male and female draft genomes of the jacky dragon Amphibolurus muricatus, an Australian dragon lizard (family Agamidae; the agamids). The assemblies are 1.8 Gb in size and have a repeat content (39%) and GC content (42%) similar to other dragon lizards. The longest scaffold was 39.7 Mb (female) and 9.6 Mb (male), with corresponding scaffold N50 values of 6.8 Mb and 1.6 Mb. The BUSCO (Sauropsida database) completeness percentages were 90.2% and 88.8% respectively. Phylogenetic comparisons show that Australian and Asian agamids split from a common ancestor about 80 million years ago, while the Australian genera Amphibolurus, Pogona, and the basal Intellagama split [~]37 million years ago. The draft A. muricatus assemblies will be a valuable resource for understanding lizard sex determination and the evolution and conservation of Australian dragon lizards.

genomics↗

bioRxiv2021

Double-stranded RNA drives SARS-CoV-2 nucleocapsid protein to undergo phase separation at specific temperatures

Betacoronavirus SARS-CoV-2 infections caused the global Covid-19 pandemic. The nucleocapsid protein (N-protein) is required for multiple steps in the betacoronavirus replication cycle. SARS-CoV-2-N-protein is known to undergo liquid-liquid phase separation (LLPS) with specific RNAs at particular temperatures to form condensates. We show that N-protein recognizes at least two separate and distinct RNA motifs, both of which require double-stranded RNA (dsRNA) for LLPS. These motifs are separately recognized by N-proteins two RNA binding domains (RBDs). Addition of dsRNA accelerates and modifies N-protein LLPS in vitro and in cells and controls the temperature condensates form. The abundance of dsRNA tunes N-protein-mediated translational repression and may confer a switch from translation to genome packaging. Thus, N-proteins two RBDs interact with separate dsRNA motifs, and these interactions impart distinct droplet properties that can support multiple viral functions. These experiments demonstrate a paradigm of how RNA structure can control the properties of biomolecular condensates.

molecular biology↗

bioRxiv2021

A gene duplication of a septin provides a developmentally-regulated filament length control mechanism

Septins are a family of conserved filament-forming proteins that function in a variety of processes including cell cycle progression, cell morphogenesis and autophagy. Despite their conservation from yeast to humans, the number of septin genes within an organism varies and higher eukaryotes express many septin isoforms due to alternative splicing. It is unclear how variability in septin complex composition influences the biophysical properties of septin polymers. Here we report that a complex duplication event within the CDC11 locus in the fungus, Ashbya gossypii, gave rise to two similar, but distinct Cdc11 proteins, Cdc11a and Cdc1b. CDC11b transcription is developmentally regulated producing different ratios of Cdc11a and b complexes during Ashbyas lifecycle. Moreover, deletion of either CDC11a or CDC11b results in distinct cell polarity defects. Remarkably, despite substantial identity in amino acid sequence, Cdc11a and Cdc11b complexes have distinct biophysical properties with clear filament length and membrane-binding ability differences. Thus, septin subunit composition has functional consequences for filament properties and such functional plasticity can be exploited for distinct biophysical properties and cell functions.

cell biology↗

bioRxiv2021

Membrane surfaces regulate assembly of a ribonucleoprotein condensate

Biomolecular condensates organize biochemistry in time and space, yet little is known about how cells control either the position or scale of these assemblies. In cells, condensates often appear as dispersed, relatively small assemblies that do not grow (coarsen) into a single droplet despite their propensity to coalesce. Here we report that ribonucleoprotein condensates of the Q-rich protein Whi3 interact with the endoplasmic reticulum, prompting us to hypothesize that membrane association controls the position and size of condensates. Reconstitution of Whi3 condensates on supported lipid bilayers reveals that association with a diffusive lipid surface promotes condensation at both physiological ionic strength and protein concentration. Notably, these assemblies rapidly arrest, matching size distributions seen in cells. The timing of the arrest is influenced by the ordering of protein-protein and protein-RNA interactions and controlled by the slow diffusion of complexes induced by the membrane. This slowed diffusion limits both transfer of small protein-RNA complexes between condensates and their coalescence, thus driving coarsening to arrest. Our experiments reveal a tradeoff between locally-enhanced protein concentration at membranes, which favors condensation, and an accompanying reduction in diffusion, which restricts coarsening. Thus, membranes can maintain a population of small condensates in the absence of active mechanisms. Given that many condensates are bound to endomembranes, we predict that the biophysical properties of lipid bilayers are key for controlling condensate sizes throughout the cell. One sentence summaryAssembly on a membrane surface positions and scales biomolecular condensates by controlling relative diffusion rates of proteins and nucleic acids.

biophysics↗

bioRxiv2021

Negative regulation of a ribonucleoprotein condensate driven by dilute phase oligomerization

Ribonucleoprotein bodies are exemplars of membraneless biomolecular condensates that can form via spontaneous or driven phase transitions. The fungal protein Whi3 forms ribonucleoprotein condensates with different RNA molecules, and these condensates are implicated in key processes such as cell-cycle control and generating cell polarity. Whi3 has a modular architecture that includes a Q-rich intrinsically disordered region (IDR) and a tandem RNA recognition module. Here, we demonstrate that a 21-residue stretch within the Q-rich IDR has a weak intrinsic preference for forming alpha-helical conformations. Through mutagenesis, we find that increased alpha helicity enhances oligomerization in the dilute phase. One consequence of enhanced oligomerization is a dilution of Whi3 in the dense phase. The opposite behavior is observed when helicity within the 21-residue stretch of the Q-rich region is abrogated. Thus, the formation of dilute phase oligomers, driven by a specific sequence motif and potential synergies with the rest of the IDR, opposes incorporation of the Whi3 protein into the dense phase, thereby altering the dense phase stoichiometry of protein to RNA. Our findings, which stand in contrast to other systems where oligomerization has been shown to enhance the drive for phase separation, point to a novel mechanism that might be operative for influencing compositions of condensates. Our work also points to routes for designing synthetic ribonucleoprotein condensates whereby modulation of protein oligomerization via homotypic interactions can impact dense phase concentrations, stoichiometries, and material properties. SignificanceA large sub-class of biomolecular condensates are linked to RNA regulation and are known as ribonucleoprotein (RNP) bodies. While extensive work has identified driving forces for biomolecular condensate formation, relatively little is known about forces that oppose assembly. Here, using a fungal RNP protein, Whi3, we show that a portion of its intrinsically disordered, glutamine-rich region modulates phase separation by forming transient alpha helical structures that promote the assembly of dilute phase oligomers. These oligomers detour Whi3 proteins from condensates, thereby impacting the driving forces for phase separation, the protein-to-RNA ratio in condensates, and the material properties of condensates. Our findings show how nanoscale conformational and oligomerization equilibria can influence mesoscale phase equilibria.

biophysics↗