Biology subjects

Li, D.

Publications and source records attributed to Li, D..

At least 325 records · Page 18Linked to original sources

bioRxiv2023

Lipid scrambling is a general feature of protein insertases

Glycerophospholipids are synthesized primarily in the cytosolic leaflet of the endoplasmic reticulum (ER) membrane and must be equilibrated between bilayer leaflets to allow the ER and membranes derived from it to grow. Lipid equilibration is facilitated by integral membrane proteins called "scramblases". These proteins feature a hydrophilic groove allowing the polar heads of lipids to traverse the hydrophobic membrane interior, similar to a credit-card moving through a reader. Nevertheless, despite their fundamental role in membrane expansion and dynamics, the identity of most scramblases has remained elusive. Here, combining biochemical reconstitution and molecular dynamics simulations, we show that lipid scrambling is a general feature of protein insertases, integral membrane proteins which insert polypeptide chains into membranes of the ER and organelles disconnected from vesicle trafficking. Our data indicate that lipid scrambling occurs in the same hydrophilic channel through which protein insertion takes place, and that scrambling is abolished in the presence of nascent polypeptide chains. We propose that protein insertases could have a so-far overlooked role in membrane dynamics as scramblases.

cell biology↗

bioRxiv2023

ZC3H11A mutations cause high myopia by triggering PI3K-AKT and NF-κB mediated inflammatory reactions in humans and mice

High myopia (HM) is a severe form of refractive error that results in irreversible visual impairment and even blindness. However, the genetic and pathological mechanisms underlying this condition are not yet fully understood. From a cohort of 1015 patients with high myopia in adolescents, likely pathogenic missense mutations were identified in the ZC3H11A gene in four patients by whole exome sequencing. This gene is a zinc finger and stress-induced protein that plays a significant role in regulating nuclear mRNA export. To better understand the function and molecular pathogenesis of myopia in relation to gene mutations, a Zc3h11a knock-out (KO) mouse model was created. The heterozygous KO (Het-KO) mice exhibited significant shifts in refraction towards myopia. Myopia-related factors, including TGF-{beta}1, MMP-2 and IL-6 were found to be upregulated in the retina or sclera, and electroretinography and immunofluorescence staining results showed dysfunction and reduced number of bipolar cells in the retina. Transmission electron microscopy findings suggesting ultrastructural abnormalities of the retina and sclera. Retinal transcriptome sequencing showed that 769 genes were differentially expressed, and Zc3h11a was found to have a negative impact on the PI3K-AKT and NF-{kappa}B signaling pathways by quantitative PCR and western blotting. In summary, this study characterized a new candidate pathogenic gene associated with high myopia, and indicated that the ZC3H11A protein may serve as a stress-induced nuclear response trigger, and its abnormality causes disturbances in a series of inflammatory and myopic factors. These findings offer potential therapeutic intervention targets for controlling the development of HM.

genetics↗

bioRxiv2023

Different coexistence patterns between apex carnivores and mesocarnivores based on temporal, spatial, and dietary niche partitioning analysis in Qilian Mountain National Park, China

Carnivores play key roles in maintaining ecosystem structure and function as well as ecological processes. Understanding how sympatric species coexist in natural ecosystems is a central research topic in community ecology and biodiversity conservation. In this study, we explored intra- and interspecific niche partitioning along spatial, temporal, and dietary niche partitioning between apex carnivores (wolf Canis lupus, snow leopard Panthera uncia, Eurasian lynx Lynx lynx) and mesocarnivores (Pallass cat Otocolobus manul, red fox Vulpes vulpes, Tibetan fox Vulpes ferrilata) in Qilian Mountain National Park, China using camera trapping data and DNA metabarcoding sequencing data. Our study showed that apex carnivore species had more overlap temporally (coefficients of interspecific overlap ranging from 0.661 to 0.900) or trophically (Piankas index ranging from 0.458 to 0.892), mesocarnivore species had high dietary overlap with each other (Piankas index ranging from 0.945 to 0.997), and apex carnivore and mesocarnivore species had high temporal overlap (coefficients of interspecific overlap ranging from 0.497 to 0.855). Large dietary overlap was observed between wolf and snow leopard (Piankas index=0.892) and Pallass cat and Tibetan fox (Piankas index=0.997), suggesting the potential for increased resource competition for these species pairs. We concluded that spatial niche partitioning is likely to key driver in facilitating the coexistence of apex carnivore species, while spatial and temporal niche partitioning likely facilitate the coexistence of mesocarnivore species, and spatial and dietary niche partitioning facilitate the coexistence between apex and mesocarnivore species. Our findings consider partitioning across temporal, spatial and dietary dimensions while examining diverse coexistence patterns of carnivore species in Qilian Mountain National Park, China. These findings will contribute substantially to current understanding of carnivore guilds and effective conservation management in fragile alpine ecosystems.

ecology↗

bioRxiv2023

Robust and resource-optimal dynamic pattern formation of Min proteins in vivo

The Min system in Escherichia coli plays a crucial role in cellular reproduction by preventing minicell formation through pole-to-pole oscillations. Despite extensive research, predicting the onset of Min protein concentrations for oscillation and understanding the systems robustness under physiological perturbations remains challenging. Our study aims to address these gaps. We show that the Min systems dynamic pattern formation is robust across a wide range of Min protein levels and varying growth physiology. Using genetically engineered E. coli strains, we independently modulated the expression of minCD and minE in E. coli under both fast and slow growth conditions. This led to the construction of a MinD-MinE phase diagram, which revealed not just a large oscillation regime but also complex dynamic patterns such as traveling and standing waves. Interestingly, we found that the natural expression level of Min proteins is nearly optimal. Our work combines experimental findings with biophysical theory based on reaction-diffusion models, reproducing the experimental phase diagram and other key properties quantitatively. This includes the observation of an invariant wavelength of dynamic Min patterns across our phase diagram. Crucially, the success of our model depends on the switching of MinE between its latent and active states, indicating its essential role as a robustness module for Min oscillation in vivo. Our results underline the potential of integrating quantitative cell physiology and biophysical modeling in understanding the fundamental mechanisms controlling cell division machinery, offering insights applicable to other biological processes.

biophysics↗

bioRxiv2023

Blood-based Nano-QuIC: Accelerated and Inhibitor-resistant Detection of Misfolded Alpha-synuclein

A hallmark of -synucleinopathies (e.g. Parkinsons disease) is the misfolding and aggregation of -synuclein in tissues and biological fluids. Protein amplification assays like real-time quaking-induced conversion (RT-QuIC) are sensitive yet currently limited to semi-invasive sample types such as cerebrospinal fluid because more accessible samples, such as blood, contain inhibitors. Here, we show that Nanoparticle-enhanced Quaking-induced Conversion (Nano-QuIC) can double the speed of reactions spiked with misfolded -synuclein while increasing sensitivity 100-fold in human plasma. Nano-QuIC detected spike concentrations down to 90 pg/ml in lysed whole blood, while reactions without nanoparticles (RT-QuIC) failed to have any detection due to the presence of strong inhibitors. Moreover, Nano-QuIC showed increased seeding activity in plasma samples from Parkinsons patients (n=4) versus healthy controls (n=4). This sets the groundwork for the noninvasive diagnostic use of Nano-QuIC, potentially enabling early disease detection and management through blood-based testing. TOC graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/552630v2_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1141573org.highwire.dtl.DTLVardef@18c63d6org.highwire.dtl.DTLVardef@1ee9524org.highwire.dtl.DTLVardef@81af13_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Lactate activates the mitochondrial electron transport chain independent of its metabolism

Lactate has long been considered a cellular waste product. However, we found that as extracellular lactate accumulates, it also enters the mitochondrial matrix and stimulates mitochondrial electron transport chain (ETC) activity. The resulting increase in mitochondrial ATP synthesis suppresses glycolysis and increases the utilization of pyruvate and/or alternative respiratory substrates. The ability of lactate to increase oxidative phosphorylation does not depend on its metabolism. Both L- and D-lactate are effective at enhancing ETC activity and suppressing glycolysis. Furthermore, the selective induction of mitochondrial oxidative phosphorylation by unmetabolized D-lactate reversibly suppressed aerobic glycolysis in both cancer cell lines and proliferating primary cells in an ATP-dependent manner and enabled cell growth on respiratory-dependent bioenergetic substrates. In primary T cells, D-lactate enhanced cell proliferation and effector function. Together, these findings demonstrate that lactate is a critical regulator of the ability of mitochondrial oxidative phosphorylation to suppress glucose fermentation.

cell biology↗

bioRxiv2023

Functional traits fail to predict long-term responses to climate change

AimEnvironmental conditions strongly affect the distribution and abundance of species via complex forces. Shifts in environmental conditions and differences in the speed and scale of these effects complicate our efforts to infer how species will respond to future environmental change. We test how 18 functional traits affect plant species responses to gradients in environmental conditions and 50-year shifts in climate. LocationWe analyzed 50-year shifts in the distribution and abundance of 153 plant species distributed across 284 sites in Wisconsin, USA. Time period1950s to 2000s. Major taxa studiedVascular plants (much of the flora of NE North America). MethodsWe used random forest and integrated hierarchical mixed models to test how plant abundances (and 50-year changes in abundance) track gradients in overstory, soil, and climatic conditions. ResultsWithin study periods, plant abundances reflect gradients in environmental conditions. Leaf traits affected local abundance (both directly and via trait-environment interactions) in the 1950s and 2000s. Strong soil and temperature effects in the 1950s have weakened while precipitation effects have strengthened. Although we expected these models to also predict how plants would respond to shifts in climate, they did not. Main conclusionsLags in species responses, increases in the stochastic forces affecting community assembly, and other forces limit the ability of models fitted to static data (e.g., space-for-time substitutions) to predict how plant species will respond to long-term shifts in environmental conditions. We must therefore be cautious about applying trait-based species distribution models to predict how climate change will affect species distributions and community structure.

ecology↗

bioRxiv2023

Classification of helical polymers with deep-learning language models

Many macromolecules in biological systems exist in the form of helical polymers. However, the inherent polymorphism and heterogeneity of samples complicate the reconstruction of helical polymers from cryo-EM images. Currently available 2D classification methods are effective at separating particles of interest from contaminants, but they do not effectively differentiate between polymorphs, resulting in heterogeneity in the 2D classes. As such, it is crucial to develop a method that can computationally divide a dataset of polymorphic helical structures into homogenous subsets. In this work, we utilized deep-learning language models to embed the filaments as vectors in hyperspace and group them into clusters. Tests with both simulated and experimental datasets have demonstrated that our method - HLM (Helical classification with Language Model) can effectively distinguish different types of filaments, in the presence of many contaminants and low signal-to-noise ratios. We also demonstrate that HLM can isolate homogeneous subsets of particles from a publicly available dataset, resulting in the discovery of a previously unknown non-proteinaceous density around tau filaments.

biophysics↗

bioRxiv2023

Disease-specific tau filaments assemble via polymorphic intermediates

Intermediate species in the assembly of amyloid filaments are believed to play a central role in neurodegenerative diseases and may constitute important targets for therapeutic intervention. However, structural information about intermediate species has been scarce and the molecular mechanisms by which amyloids assemble remain largely unknown. Here, we use time-resolved electron cryo-microscopy (cryo-EM) to study the in vitro assembly of recombinant truncated tau (amino acids 297-391) into paired helical filaments of Alzheimers disease or into filaments of chronic traumatic encephalopathy. We report the formation of a shared first intermediate amyloid (FIA), with an ordered core comprising amino acids 302-316. Nuclear magnetic resonance indicates that the same amino acids adopt rigid, {beta}-strand-like conformations in monomeric tau. At later time points, the FIAs disappear and we observe many different intermediate amyloid filaments, with structures that depend on the reaction conditions. At the end of both reactions, most intermediate amyloids disappear and filaments with the same ordered cores as those from human brains remain. Our results provide structural insights into the processes of primary and secondary nucleation of amyloid assembly, with implications for the design of novel therapies.

biophysics↗

bioRxiv2023

Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions

Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing yet it protected mice and cynomolgus macaques from severe disease. The mechanisms of this non-neutralizing antibody-mediated protection are unknown. Here we show that Fc effector functions mediate non-neutralizing antibody (non-nAb) protection against SARS-CoV-2 MA10 viral challenge in mice. Though non-nAb infusion did not suppress infectious viral titers in the lung as potently as NTD neutralizing antibody (nAb) infusion, disease markers including gross lung discoloration were similar in nAb and non-nAb groups. Fc functional knockout substitutions abolished non-nAb protection and increased viral titers in the nAb group. Finally, Fc enhancement increased non-nAb protection relative to WT, supporting a positive association between Fc functionality and degree of protection in SARS-CoV-2 infection. This study demonstrates that non-nAbs can utilize Fc-mediated mechanisms to lower viral load and prevent lung damage due to coronavirus infection. AUTHOR SUMMARYCOVID-19 has claimed over 6.8 million lives worldwide and caused economic and social disruption globally. Preventing more deaths from COVID-19 is a principal goal of antibody biologic and vaccine developers. To guide design of such countermeasures, an understanding of how the immune system prevents severe COVID-19 disease is needed. We demonstrate here that antibody functions other than neutralization can contribute to protection from severe disease. Specifically, the functions of antibodies that rely on its Fc portion were shown to confer antibody-mediated protection of mice challenged with a mouse adapted version of SARS-CoV-2. Mice given an antibody that could not neutralize SARS-CoV-2 still showed a decrease in the amount of infectious virus in the lungs and less lung damage than mice given an irrelevant antibody. The decrease in infectious virus in the lungs was even larger when the non-neutralizing antibody was engineered to mediate non-neutralizing effector functions such as antibody-dependent cellular cytotoxicity more potently. Thus, in the absence of neutralization activity, non-neutralizing binding antibodies can contribute to the overall defense against SARS-CoV-2 infection and COVID-19 disease progression.

immunology↗

bioRxiv2023

Modeling Human Spine-Spinal Cord Organogenesis by hPSC-Derived Neuromesodermal Progenitors

Human trunk development, including spine and spinal cord organogenesis, is a coordinated, orderly, and interdependent process with spatiotemporal tissue patterning. However, the underlying cellular and molecular mechanisms remain largely unclear due to the lack of an effective model that can simulate the early development of human body axis. Here, we reported the long-term patterning and dynamic morphogenesis of human trunk through the formation of spine-spinal cord organoids (SSCOs) self-organized from three-dimensional culture of human PSC-derived neuromesodermal progenitors (NMPs). The SSCOs resembled the morphogenetic features of spine and spinal cord along the anterior-posterior axis, and showed the chondro-osteogenic and neural trajectories consistent with developmental dynamics of spine and spinal cord in gestational embryo through single-cell RNA sequencing (scRNA-seq). In addition, we identified a new HMMR+ bipotent cell population with self-renewal ability and neural/mesodermal competence but distinct from NMPs, which may be involved in trunk development and represent an invaluable tool for disease modeling of spine- and spinal cord-related disorders. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/549829v1_ufig1.gif" ALT="Figure 1"> View larger version (80K): org.highwire.dtl.DTLVardef@14bfd30org.highwire.dtl.DTLVardef@1db7fe8org.highwire.dtl.DTLVardef@1aa66a1org.highwire.dtl.DTLVardef@380932_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2023

A Plant Flavonol Rescues a Pathogenic Mutation Associated with Kinesin in Neurons

KIF1A, a microtubule-based motor protein responsible for axonal transport, is linked to a group of neurological disorders known as KIF1A-associated neurological disorder (KAND). Current therapeutic options for KAND are limited. Here, we introduced the clinically relevant KIF1A(R11Q) variant into the C. elegans homolog UNC-104, resulting in uncoordinated animal behaviors. Through genetic suppressor screens, we identified intragenic mutations in UNC-104s motor domain that rescued synaptic vesicle localization and coordinated movement. We showed that two suppressor mutations partially recovered motor activity in vitro by counteracting the structural defect caused by R11Q at KIF1As nucleotide-binding pocket. We found that supplementation with fisetin, a plant flavonol, improved KIF1A(R11Q) worms movement and morphology. Notably, our biochemical and single-molecule assays revealed that fisetin directly restored the ATPase activity and processive movement of human KIF1A(R11Q) without affecting wild-type KIF1A. These findings suggest fisetin as a potential intervention for enhancing KIF1A(R11Q) activity and alleviating associated defects in KAND.

cell biology↗

bioRxiv2023

DICTrank: The largest reference list of 1318 human drugs ranked by risk of drug-induced cardiotoxicity using FDA labeling

Drug-induced cardiotoxicity (DICT) is one of the leading causes of drug attrition in clinical trials or withdrawal from the market. Many studies have been conducted to detect DICT in the early stage of drug development and clinical diagnosis, but the success is limited, as evident by the high attrition rate at all clinical phases due to DICT. Most of these efforts, if not all, have focused on specific adverse events and/or mechanisms associated with DICT, such as QT prolongation and hERG-related cardiotoxicity. However, given the broad spectrum of cardiotoxicity, it is necessary to develop a reference drug list with a systematic annotation of DICT potential across a large number of drugs and drug classes. Such a list is essential for developing effective DICT diagnostic biomarkers and early prediction strategies using new approach methods (NAMs), including artificial intelligence (AI). By utilizing labeling documents for FDA (U.S. Food and Drug Administration)-approved drugs, we developed a drug classification scheme to prioritize drugs based on their DICT potential. This resulted in DICTrank, which is the largest dataset of drugs annotated with ranked DICT risk in humans. DICTrank categorizes drugs into four categories of DICT concerns by integrating DICT severity and labeling content. The dataset consists of 1318 drugs, classified as follows: Most-DICT-Concern (341), Less-DICT-Concern (528), No-DICT-Concern (343), and Ambiguous-DICT-Concern (106; lacking sufficient information in the labeling document to determine cardiotoxicity potential). DICTrank covers a wide range of drug therapeutic categories. Using this extensive DICT dataset, we discovered that several therapeutic categories were significantly enriched with drugs of Most-DICT-Concern as well as the association of daily dose with drug class. These categories include antineoplastic agents, sex hormones and modulators of the genital system, anti-inflammatory and antirheumatic products, beta-blocking agents, and cardiac therapy. DICTrank represents the largest drug list for DICT to date, and it could contribute to the development of NAMs and AI models for the early identification of DICT risk during drug development and beyond.

pharmacology and toxicology↗

bioRxiv2023

Transcriptome brings variations of gene expression, alternative splicing, and structural variations into gene-scale trait dissection in soybean

Genome-wide association study (GWAS) identifies trait-associated loci, but due in part to slow decay of linkage disequilibrium (LD), identifying the causal genes can be a bottleneck. Transcriptome-wide association study (TWAS) addresses this by identifying gene expression-phenotype associations or integrating gene expression quantitative trait loci (eQTLs) with GWAS results. Here, we used self-pollinated soybean as a model to evaluate the application of TWAS in the genetic dissection of traits in plant species that exhibit slow LD decay. The first RNA-Seq analysis of a soybean diversity panel was conducted, which identified the genetic regulation of 29,286 genes. Different TWAS solutions were less affected by LD and robust with source of expression that identified known genes related to traits from different development stages and tissues. A novel gene named pod color L2 was identified via TWAS and functionally validated by genome editing. Our introduction of the new exon proportion feature significantly improves the capture of expression variations resulting from structural variations and alternative splicing. As a result, the genes identified by our TWAS approach exhibited a diverse range of causal variations, including SNP, insertion/deletion, gene fusion, copy number variation, and alternative splicing. Using our TWAS approach, we identified genes associated with flowering time, including both previously known candidates and novel genes that had not been linked to this trait before, providing complementary insights with GWAS. In summary, this study supports the application of TWAS for candidate gene identification in species with low rates of LD decay.

genetics↗

bioRxiv2023

Phosphorylation and O-GlcNAcylation at the same alpha-synuclein site generate distinct fibril structures

-Synuclein (-syn) forms amyloid fibrils that are critical in the progression of Parkinsons disease (PD) and serves as the pathological hallmark of PD. Different posttranslational modifications (PTMs) have been identified at multiple sites of -syn, influencing its conformation, aggregation and function. Here, we investigate how disease-related phosphorylation and O-GlcNAcylation at the same -syn site (S87) affect fibril structure and neuropathology. Using semi-synthesis, we obtained homogenous -syn monomer with site-specific phosphorylation (pS87) and O-GlcNAcylation (gS87) at S87, respectively. Cryo-EM analysis revealed that pS87 and gS87 -syn form two novel but distinct fibril structures. The GlcNAc situated at S87 establishes interactions with K80 and E61, inducing a unique iron-like fold with the GlcNAc molecule on the iron handle. While, phosphorylation at the same site prevents a lengthy C-terminal region including residues 73-140 from incorporating into the fibril core due to electrostatic repulsion. Instead, the N-terminal half (1-72) shapes a novel arch-like fibril structure. We further show that both pS87 and gS87 -syn fibrils display reduced neurotoxicity and propagation activity compared with unmodified -syn fibril. Our findings demonstrate that different PTMs at the same site can produce distinct fibril structures, which emphasizes the precise regulation of PTMs to amyloid fibril formation and pathology.

biochemistry↗

bioRxiv2023

Mammalian PIWI-piRNA-target complexes reveal features for broad and efficient target-silencing

The PIWI-interacting RNA (piRNA) pathway is an adaptive defense system wherein piRNAs guide PIWI-family Argonaute proteins to recognize and silence ever-evolving selfish genetic elements and ensure genome integrity. Driven by this intensive host-pathogen arms race, piRNA pathway and its targeted transposons have co-evolved rapidly in a species-specific manner, but how the piRNA pathway specifically adapts to target silencing in mammals remains elusive. Here, we show that mouse MILI and human HILI piRISCs bind and cleave targets more efficiently than their invertebrate counterpart from sponge Ephydatia fluviatilis. The inherent functional differences comport with structural features identified by cryo-EM studies of piRISCs. In the absence of target, MILI and HILI piRISCs adopt a wider nucleic-acid-binding channel and display an extended prearranged piRNA seed as compared to EfPiwi piRISC, consistent with their ability to capture targets more efficiently than EfPiwi piRISC. In the presence of target, the seed gate--which enforces seed-target fidelity in microRNA RISC--adopts a relaxed state in mammalian piRISC, revealing how MILI and HILI tolerate seed-target mismatches to broaden the target spectrum. A vertebrate-specific lysine distorts the piRNA seed, shifting the trajectory of the piRNA-target duplex out of the central cleft and toward the PAZ lobe. Functional analyses reveal that this lysine promotes target binding and cleavage. Our study therefore provides a molecular basis for the piRNA targeting mechanism in mouse and human, and suggests that mammalian piRNA machinery can achieve broad target silencing using a limited supply of piRNA species.

molecular biology↗

bioRxiv2023

ALS-causing SOD1 mutations H46R and G85R form similar novel amyloid fibril structures and promote ferroptosis in cells

More than two hundred genetic mutations of Cu, Zn-superoxide dismutase (SOD1) have been identified in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the selective death of motor neurons through ferroptosis. Two ALS-causing SOD1 mutations, H46R and G85R, are metal-binding region mutants with reduced affinity for metal ions. Here, we generated amyloid fibrils from the apo forms of H46R and G85R under reducing conditions and determined their structures using cryo-EM. We built models for the fibril cores, comprising residues 85-153 for H46R and 82-153 for G85R. These mutations disrupt crucial interactions in the wild-type SOD1 fibril, resulting in amyloid fibrils with distinct structures compared to the wild-type fibril. Remarkably, H46R and G85R form similar novel amyloid fibril structures. The fibril cores display a serpentine fold containing seven or eight {beta}-strands, which are stabilized by a hydrophobic cavity. In the G85R fibril core, Arg85 and Asp101 form a salt bridge for stabilization. We demonstrate that fibril seeds from H46R and G85R cause more severe mitochondrial impairment and significantly promote ferroptosis in neuronal cells, compared with those from wild-type SOD1. Our findings reveal how different SOD1 mutations can result in similar amyloid fibril structures and contribute to ALS pathology.

biochemistry↗

bioRxiv2023

Genome duplications, genomic conflict, and rapid phenotypic evolution characterize the Cretaceous radiation of Fagales

O_LIFlowering plant lineages display remarkable diversity in life history and morphological form. However our understanding of how this phenotypic diversity or disparity, arises and what, if any, relation there is to processes such as gene and genome duplication remains unlcear. C_LIO_LIHere we investigate the relationship between phenotypic and genomic evolution in the angiosperm order Fagales, a lineage of woody plants that has been a dominant component of temperate and subtropical forests since the Late Cretaceous. To this end, we examine newly generated trait and transcriptomic datasets spanning the phylogenetic breadth of the order, including most extant genera as well as a rich diversity of Cretaceous fossil representatives. C_LIO_LIOur phylogenomic analyses resolved the location of an ancient polyploidization event in Juglandaceae and identified hotspots of gene-duplication and genomic conflict across the order. Examinations of phenotypic evolution (including morphospace occupancy and rate shifts) show that the morphospace occupied by Fagales was filled by the early Cenozoic and rates of evolution were highest during the early radiation of the Fagales crown and its major families. Many instances of phenotypic rates also correspond to hotspots of gene duplication. C_LIO_LIOur results show that Fagales conform to an "early burst" model of phenotypic diversification, with morphospace being filled early in the groups evolutionary history. Our study is consistent with others showing a decoupling of species diversification with other biological processes (e.g., phenotypic and genomic evolution), underscoring the complexity of understanding the major drivers of plant evolution over broad timescales. C_LI

evolutionary biology↗