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At least 19 recordsLinked to original sources
PubMed2025

Cell fate specification modes shape transcriptome evolution in the highly conserved spiral cleavage.

Early animal development can be remarkably variable, influenced by lineage-specific reproductive strategies and adaptations. Yet, early embryogenesis is also strikingly conserved in certain groups, such as Spiralia. In this clade, a shared cleavage program (i.e., spiral cleavage) and similar cell lineages are ancestral to at least seven phyla. Why early development is so conserved in specific groups and plastic in others is not fully understood. Here, we investigated two annelid species (Owenia fusiformis and Capitella teleta) with spiral cleavage but different modes of specifying their primary progenitor cells. By generating high-resolution transcriptomic time courses from the oocyte to gastrulation, we demonstrate that transcriptional dynamics differ markedly between these species during spiral cleavage and instead reflect their distinct timings of embryonic organiser specification. However, the end of cleavage and gastrulation exhibit high transcriptomic similarity, when orthologous transcription factors share gene expression domains, suggesting this period is a previously overlooked mid-developmental transition in annelid embryogenesis. Together, our data reveal hidden transcriptomic plasticity during spiral cleavage, indicating an evolutionary decoupling of morphological and transcriptomic conservation during early embryogenesis.

Animals↗
PubMed2025

Recently Evolved, Stage-Specific Genes Are Enriched at Life-Stage Transitions in Flies.

Understanding how genomic information is selectively utilized across different life stages is essential for deciphering the developmental and evolutionary strategies of metazoans. In holometabolous insects, the dynamic expression of genes enables distinct functional adaptations at embryonic, larval, pupal, and adult stages, likely contributing to their evolutionary success. While Drosophila melanogaster (D. melanogaster) has been extensively studied, less is known about the evolutionary dynamics that could govern stage-specific gene expression. To address this question, we compared the distribution of stage-specific genes, that is, genes expressed in temporally restricted developmental stages, across the development of D. melanogaster and Aedes aegypti (A. aegypti). Using tau-scoring, a computational method to determine gene expression specificity, we found that, on average, a large proportion of genes (20%-30% of all protein-coding genes) in both species exhibit restricted expression to specific developmental stages. Phylostratigraphy analysis, a method to date the age of genes, further revealed that stage-specific genes fall into two major categories: highly conserved and recently evolved. Notably, many of the recently evolved and stage-specific genes identified in A. aegypti and D. melanogaster are restricted to Diptera order (20%-35% of all stage-specific genes), highlighting ongoing evolutionary processes that continue to shape life-stage transitions. Overall, our findings underscore the complex interplay between gene evolutionary age, expression specificity, and morphological transformations in development. These results suggest that the attraction of genes to critical life-stage transitions is an ongoing process that may not be constant across evolutionary time or uniform between different lineages, offering new insights into the adaptability and diversification of dipteran genomes.

Animals↗
PubMed2025

A Functionally Conserved yet Dynamically Evolving Toolkit Underpinning Molluscan Biomineralization: Insights From Shell and Radula.

The molluscan shell and radula constitute pivotal molluscan innovations, each characterized by distinct functions and diverse forms, regulated by the highly specific biomineralization regulatory networks. Despite their paramount importance, the conserved components and adaptive evolutionary processes governing these regulatory networks remain unresolved. To address this knowledge gap, we advocate for the integration of data from less-explored lineages, such as Scaphopoda, as an essential step. This study presents the inaugural comprehensive transcriptome analysis of Pictodentalium vernedei, a representative species of Scaphopoda distinguished by a unique and evolutionarily conserved shell morphology and radula structure. Furthermore, comparative transcriptome/genome analyses are employed to unravel the conservatism and evolutionary innovation of the involved biomineralization regulatory elements. Our findings underscore the central role of secretomes in governing biomineralization processes, and we identified a fundamental set of 26 domains within molluscan secretomes, forming an essential functional protein domain repertoire necessary for the transformation of inorganic ions into biomineralized structures. This core biomineralization toolkit has undergone independent expansion and lineage-specific recruitment, giving rise to novel, modular domain architectures. This may be essential for the functional specialization and morphological diversification of shell and radula structures. These evolutionary processes are driven by the independent co-option of ancient genes and the emergence of novel de novo genes. This comprehensive investigation not only contributes insights into the evolution of molluscan biomineralization structures but also establishes avenues for further scholarly exploration.

Animals↗
PubMed2026

From wild to domestic: Single-cell transcriptomic perspectives on hippocampal regulation and evolution.

How domestication shapes brain evolution remains an open question. In this study, we integrated single-nucleus RNA sequencing (snRNA-seq), population genomics, and machine learning to investigate the hippocampal evolution under domestication. Across-species comparisons revealed that hippocampal cell type profiles are largely conserved across vertebrate species, while supporting the presence of adult hippocampal neurogenesis in birds. We further found that domestication and selective breeding likely influence the cellular composition and molecular regulation of the hippocampus. Our findings provide cellular evidence supporting the hypothesis that domestication affects adult hippocampal neurogenesis. Additionally, we showed that genes associated with neural progenitor cells (NPC) states and cell-marker programs are enriched for signatures of selection. Many of these genes function as regulators of neurogenesis and pathways mediating stress and fear reduction. Specifically, we identified selection at the FKBP5 promoter that may influence its expression in the NPC lineage, potentially contributing to stress-response regulation during domestication. Collectively, these results suggest that domestication is associated with hippocampal remodeling as part of an adaptive response to human-managed environments. This study provides a cellular and genetic perspective on how domestication reshapes the brain and offers a basis for further investigation into the mechanisms of neural evolution within the context of microevolution.

Animals↗
PubMed2026

Evolution after whole-genome duplication (WGD) drives phenotypic and transcriptomic divergence more than WGD in an autopolyploid herb.

Whole-genome duplication (WGD) is a major driver of plant speciation and often hypothesized to promote rapid adaptation to new or changing environmental conditions. However, the extent to which WGD per se fosters phenotypic and transcriptional novelties, and the relative contribution of WGD-induced changes vs post-WGD evolution to trait differentiation between cytotypes remains poorly understood. Here, we investigated the phenotypic and transcriptomic consequences of WGD and subsequent evolution in the Biscutella laevigata diploid-autotetraploid complex by comparing replicated diploid, synthetic autotetraploids, and natural autotetraploids (originated some 24,000 to 7,000 generations ago) under moderate daily temperature fluctuations (stable) vs. daily heat stress (changing) conditions. WGD led to reduced specific leaf area and slower rosette growth but had no significant effect on biomass. Post-WGD evolution acted in contrasting directions on WGD-induced changes, either reverting traits to diploid-like values or maintaining them in natural autotetraploids. Overall, WGD induced a decrease in fitness that was mitigated by post-WGD evolution, resulting in natural autotetraploids with similar or higher fitness under changing conditions than diploids. While the genetic background modulates the effects of WGD, cytotype-level transcriptomic analyses revealed limited immediate effects of WGD under stable conditions, although heat stress induced different responses across cytotypes. Altogether, our results highlight a complex interplay between immediate WGD-induced and subsequent evolution at the phenotypic and transcriptomic levels, supporting a predominant role of post-WGD evolution in the differentiation of current cytotypes and the adaptive evolution of autotetraploids of B. laevigata.

Genome, Plant↗
PubMed2026

Suppression of HIV-1 replication in CEM-A cell cultures by trans-splicing group I introns targeting PAS/PBS sequences and conditionally expressing ΔN-Bax.

Anti-HIV group I introns containing antisense guide sequences directed against the HIV-1 primer activation signal and primer-binding site (PAS/PBS) were designed and evaluated. Because PAS/PBS sequences are present in the viral RNA species examined, these RNAs can serve as trans-splicing substrates. The introns were active against both artificial target RNAs and viral RNA generated during infection. Cleavage and degradation of targeted viral RNA may have contributed to suppression, whereas inclusion of a 3' exon encoding the proapoptotic protein ΔN-Bax was associated with increased programmed cell death and may have augmented suppression of viral replication. In cultured CEM-A cells, transgene expression of these introns markedly suppressed HIV-1 replication, with p24 levels falling below the assay detection limit in selected clones. RESULTS: RT-PCR and sequence analysis detected splice products containing the expected PAS/PBS junctions. In the dual-luciferase assay, intron expression reduced normalized Gaussia luciferase signal by approximately 70% relative to the negative control. Qualitative Annexin V imaging and caspase-3 assays were consistent with infection-dependent apoptosis after ΔN-Bax splice-product formation. Transient expression of each intron in HEK293T cells followed by infection with VSV-G-pseudotyped HIV-1NL4-3 at an MOI of 2 reduced p24 levels by approximately 50% at 4 days post-infection. Construct 128L produced the strongest RT-PCR band under the tested conditions and was selected for subsequent experiments. A canonical splice product and a low-abundance noncanonical splice product were detected; both involved the intended HIV-derived target RNA, although transcriptome-wide off-target splicing was not assessed. Heterogeneous transformed HEK293T populations showed an approximately 2-log10 reduction in p24. In selected clonal HEK293T and CEM-A lines, p24 was below the assay detection limit at the measured endpoints, including up to 90 days after infection in some CEM-A clones. CONCLUSIONS: PAS/PBS-targeting group I introns suppressed HIV-1-associated p24 production in the tested cell-culture models. Linking the introns to a ΔN-Bax 3' exon was associated with infection-dependent apoptosis and may further limit viral replication and spread. The use of highly conserved, functionally constrained target sequences may reduce the likelihood of escape, but viral evolution and transcriptome-wide off-target effects were not assessed. This conditional death-upon-infection strategy warrants further evaluation in primary-cell and in vivo models.

Humans↗
PubMed2026

Transcriptome mining and comparative genomics reveal 36 putative novel marafivirus species and conserved evolution of the marafibox regulatory element.

BACKGROUND: Marafiviruses are plant-infecting RNA viruses associated with several economically important crops, but their genomic diversity remains incompletely characterized. OBJECTIVE: This study aimed to identify previously unrecognized marafivirus genomes and investigate their genomic features and evolutionary relationships. METHODS: Publicly available plant transcriptome datasets were systematically mined to detect marafivirus-like sequences. Recovered genomes were analyzed using comparative sequence analysis, phylogenetic reconstruction, and genome organization characterization. RESULTS: A total of 62 marafivirus-like genomes were recovered from 33 independent sources representing diverse plant hosts. Polyprotein-based comparative and phylogenetic analyses grouped these genomes into 36 lineages likely representing novel species. All newly identified viruses clustered within the Marafivirus clade. Genome organization analysis revealed conserved polyprotein architecture and widespread presence of the marafibox promoter element. Conservation of additional open reading frames among closely related isolates aided identification of potentially functional genes. CONCLUSION: These findings substantially expand the known diversity of marafiviruses and demonstrate the effectiveness of transcriptome mining for discovering previously unrecognized plant viruses.

Phylogeny↗
PubMed2026

The evolution of Ca2+-ATPases across plants with profiles in Rhododendron and the function of key members in alleviating high calcium stress.

Ca2+-ATPase (CAP) is a key Ca2+ efflux protein in plants. Our previous research suggests that CAPs may play a crucial role in the adaptation of rhododendrons to high calcium environments. However, the evolution, variation, characteristic expression, and subfunctionalization of this gene family in Rhododendron remain unknown. Through the analysis of pan-genomes and pan-transcriptomes, we elucidated the systematic evolution of CAPs in plants, as well as their characteristic expression patterns in Rhododendron. During the evolutionary process from lower to higher plants, CAPs can be divided into six clades and exhibit structural conservation. CAPs have emerged and differentiated in lower plants such as algae, and they have undergone significant amplification in Eudicots plants like rhododendrons. Three Rhododendron species (Rhododendron bailiense, R. delavayi, and R. irroratum) located in the karst province of Guizhou in Southwest China exhibit the highest copies of CAPs, suggesting a strong association between CAP copy number variation and habitat, particularly in high calcium environments. Through multiple transcriptome analyses, we revealed that CAPs are induced under various environmental/developmental conditions (e.g. karst environments, high altitude, early flower development, hormones, etc.). Co-expression network analysis highlighted key members of calcineurin B-like protein (CBL) and CBL-interacting protein kinases (CIPK) that are associated with the high expression of CAPs. Experimental validation demonstrated that CAPb1 and CAPd1 significantly alleviate high calcium stress, and the CAPb1-CIPK1-CBL1 and CAPd1-CIPK2-CBL1 modules can further enhance the alleviation. These findings provide new insights into the evolution, characteristic expression, and function of CAPs, as well as new perspectives on the high calcium adaptability of rhododendrons.

Journal Article↗
PubMed2025

Adaptive Evolution for Freshwater Adaptation in Coilia nasus by Directional Selection on Osmoregulation Genes.

The molecular mechanisms underlying the adaptation to freshwater habitats in fish of marine origin remain unclear. Grenadier anchovies, such as Coilia nasus, originate from marine environments and include both anadromous and freshwater-resident conspecifics, making them ideal for studying adaptive evolution from marine to freshwater habitats. We conducted a comparative population genomic and transcriptome analysis of two distinct C. nasus lineages, one anadromous and the other freshwater-resident, collected from mainstream and estuarine regions of the Yangtze River, China. By genome-wide genotyping of the anadromous and the freshwater-resident populations, we observed significant divergence in osmoregulation, energy metabolism, and immune response pathways associated with ecological adaptation and energy expenditure for migration. Some ion transport genes such as CAMK1, ATP1α3, KCNJ1 and SLC30A2 were identified that may contribute to freshwater adaptation. Notably, numerous mineralocorticoid signalling genes (e.g., NR3C2, SGK1, ATP1α3, KCNJ1) exhibit dynamic change between the anadromous and freshwater populations, suggesting an important role for the hormone cortisol in regulating salinity acclimation in euryhaline fish. Among these genes, the ion channel ATP1α3 experienced adaptive amino acid substitutions (Val317Ile and Thr329Ser), which appear to be evolutionary hotspots across migratory species based on ortholog comparisons. These variants may facilitate sodium/potassium transport and highlight salinity tolerance as a key driver of divergence in anadromous fish transitioning to freshwater. These results enhance our understanding of the genetic basis underlying freshwater adaptation for an anadromous fish across osmotic boundaries.

Animals↗
PubMed2025

Molecular signature of primate astrocytes reveals pathways and regulatory changes contributing to human brain evolution.

Astrocytes contribute to the development and regulation of the higher-level functions of the brain, the critical targets of evolution. However, how astrocytes evolve in primates is unsettled. Here, we obtain human, chimpanzee, and macaque induced pluripotent stem-cell-derived astrocytes (iAstrocytes). Human iAstrocytes are bigger and more complex than the non-human primate iAstrocytes. We identify new loci contributing to the increased human astrocyte. We show that genes and pathways implicated in long-range intercellular signaling are activated in the human iAstrocytes and partake in controlling iAstrocyte complexity. Genes downregulated in human iAstrocytes frequently relate to neurological disorders and were decreased in adult brain samples. Through regulome analysis and machine learning, we uncover that functional activation of enhancers coincides with a previously unappreciated, pervasive gain of "stripe" transcription factor binding sites. Altogether, we reveal the transcriptomic signature of primate astrocyte evolution and a mechanism driving the acquisition of the regulatory potential of enhancers.

Astrocytes↗
PubMed2026

Spatial transcriptomics of primary and metastatic ALK-rearranged NSCLC reveals site-specific adaptations.

INTRODUCTION: Genetic alterations and the tumor microenvironment (TME) influence treatment response in anaplastic lymphoma kinase-rearranged non-small cell lung cancer (ALK+ NSCLC). This study maps site-specific TME adaptations and exploratory risk-associated signatures in lymph node metastases (LNT) to investigate metastatic evolution. METHOD: We applied spatial transcriptomics to profile tumor (PanCK+) and stromal (PanCK-) compartments in a pilot cohort of 16 cases: primary lung tumors (LT, n = 3), LNT (n = 10), and brain metastases (BT, n = 3), with three site-matched non-tumor controls. LNT-derived prognostic signatures were evaluated using The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA LUAD) cohorts. RESULTS: Distinct, site-specific TME features were observed. LNT stroma was enriched in fibroblasts and macrophages, while tumor segments showed increased neutrophils. BT exhibited a macrophage-associated immunosuppressive TME. Tumor cells evolved divergently: LT retained pulmonary identity and showed trend towards translation-associated programs, LNT cells shifted toward senescence and epigenetic remodeling, and BT cells showed activation of Class A/1 (Rhodopsin-like) receptor, GPCR and drug metabolism pathways. In LNT, exploratory risk-associated differences were observed. Low-risk cases (n = 6) showed adaptive immune signatures, whereas high-risk cases (n = 4) showed enrichment for stromal MET signaling and stress-response pathways. Because treatment exposure differed markedly between the risk groups, these observations should be interpreted as hypothesis-generating. TCGA LUAD analysis suggested the broader biological relevance of immune-associated markers, but reflected general LUAD rather than ALK+ specific biology. Discordant associations for GCLC and TIMP1 underscored the importance of spatial context. CONCLUSION: Site-specific microenvironments may influence tumor adaptation across metastatic niches in ALK+ NSCLC. The exploratory risk-associated findings require validation in larger, uniformly treated cohorts.

Humans↗
PubMed2025

Laboratory Evolution Reveals Transcriptional Mechanisms Underlying Thermal Adaptation of Escherichia coli.

Adaptive laboratory evolution is able to generate microbial strains, which exhibit extreme phenotypes, revealing fundamental biological adaptation mechanisms. Here, we use adaptive laboratory evolution to evolve Escherichia coli strains that grow at temperatures as high as 45.3 °C, a temperature lethal to wild-type cells. The strains adopted a hypermutator phenotype and employed multiple systems-level adaptations that made global analysis of the DNA mutations difficult. Given the challenge at the genomic level, we were motivated to uncover high-temperature tolerance adaptation mechanisms at the transcriptomic level. We employed independently modulated gene set (iModulon) analysis to reveal five transcriptional mechanisms underlying growth at high temperatures. These mechanisms were connected to acquired mutations, changes in transcriptome composition, sensory inputs, phenotypes, and protein structures. They are as follows: (i) downregulation of general stress responses while upregulating the specific heat stress responses, (ii) upregulation of flagellar basal bodies without upregulating motility and upregulation fimbriae, (iii) shift toward anaerobic metabolism, (iv) shift in regulation of iron uptake away from siderophore production, and (v) upregulation of yjfIJKL, a novel heat tolerance operon whose structures we predicted with AlphaFold. iModulons associated with these five mechanisms explain nearly half of all variance in the gene expression in the adapted strains. These thermotolerance strategies reveal that optimal coordination of known stress responses and metabolism can be achieved with a small number of regulatory mutations and may suggest a new role for large protein export systems. Adaptive laboratory evolution with transcriptomic characterization is a productive approach for elucidating and interpreting adaptation to otherwise lethal stresses.

Escherichia coli↗
PubMed2024

A time-resolved single-cell roadmap of the logic driving anterior neural crest diversification from neural border to migration stages.

Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of early molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification toward definitive neural crest. Here, we combine ultradense single-cell transcriptomes with machine-learning and large-scale transcriptomic and epigenomic experimental validation of selected trajectories, to provide the general principles and highlight specific features of the GRN underlying neural crest fate diversification from induction to early migration stages using Xenopus frog embryos as a model. During gastrulation, a transient neural border zone state precedes the choice between neural crest and placodes which includes multiple converging gene programs. During neurulation, transcription factor connectome, and bifurcation analyses demonstrate the early emergence of neural crest fates at the neural plate stage, alongside an unbiased multipotent-like lineage persisting until epithelial-mesenchymal transition stage. We also decipher circuits driving cranial and vagal neural crest formation and provide a broadly applicable high-throughput validation strategy for investigating single-cell transcriptomes in vertebrate GRNs in development, evolution, and disease.

Animals↗
PubMed2025

Analysis of Leishbuviridae from Trypanosomatids.

Over the last decade, considerable progress has been made in unraveling RNA virus diversity. This has contributed to our understanding of the evolution of these viruses, which include emerging zoonotic human pathogens. Current success has been greatly facilitated by the development of next-generation sequencing platforms instrumental for meta-transcriptomic studies. However, due to the rapid evolution of RNA viruses, there are numerous "blind spots" waiting to be explored; one of those is the RNA virome of unicellular eukaryotes. Here, we present the pipeline, which has been successfully used to characterize various types of RNA viruses, including Leishbuviridae (Bunyaviricetes, Hareavirales) in the parasitic flagellates of the family Trypanosomatidae. The pipeline relies on axenic in vitro cell culture and double-stranded RNA enrichment, followed by direct RNA-sequencing. A detailed procedure description starting from the initial total RNA preparation to the final assembly of the viral segments is provided.

High-Throughput Nucleotide Sequencing↗
PubMed2025

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy. We also uncover a co-evolution between the tumor and the T cell repertoire, as well as a longitudinal shift in the TME from an anti-tumor to an immunosuppressive state, linked to the acquisition of recurrently late ccRCC drivers 9p loss and SETD2 mutations. Our study reveals clinically-relevant and hitherto underappreciated non-genetic evolution patterns in ccRCC.

Journal Article↗
PubMed2025

Polyploidy-mediated variations in glutamate receptor proteins linked to Fusarium wilt resistance in upland cotton.

Cotton production in the US faces a serious threat from Fusarium oxysporum f. sp. vasinfectum race 4 (FOV4), a soil-borne fungus causing Fusarium wilt by infecting the roots and vascular system of susceptible cotton, leading to rapid wilting and death. Here, we investigate genetic mechanisms of resistance to FOV4 in the highly resistant upland cotton genotype "U1" using an early-generation segregating biparental population ("U1" × "CSX8308") with comprehensive genomic resources. Reference-grade genomic assemblies of the parents revealed minor structural variations between "U1" haplotypes, a high degree of collinearity at chromosome synteny and micro-synteny levels, and significant divergence from "CSX8308" with 8.9 million SNPs. QTL analysis identified significant markers on chromosomes D03 and A02 linked to reduced Fusarium wilt severity. Within these regions, two glutamate-receptor-like (GLR) genes showed structural variation and overlapped between translocated segments on A02 and D03, suggesting a rare but important reinforcing effect of parallel evolution between susceptible and resistant genotypes. Transcriptome profiles of "U1" under FOV4 infection reveal activation of calcium-binding proteins and transcription factors regulating plant hormones (ethylene, abscisic acid, jasmonic acid, and salicylic acid), along with enzymes involved in cell wall remodeling and phytoalexin production. Advancing cotton improvement depends on incorporating durable genetic disease resistance into high-yielding, high-quality cultivars.

Fusarium↗
PubMed2023

Developmental and genomic insight into the origin of the tardigrade body plan.

Tardigrada is an ancient lineage of miniaturized animals. As an outgroup of the well-studied Arthropoda and Onychophora, studies of tardigrades hold the potential to reveal important insights into body plan evolution in Panarthropoda. Previous studies have revealed interesting facets of tardigrade development and genomics that suggest that a highly compact body plan is a derived condition of this lineage, rather than it representing an ancestral state of Panarthropoda. This conclusion was based on studies of several species from Eutardigrada. We review these studies and expand on them by analyzing the publicly available genome and transcriptome assemblies of Echiniscus testudo, a representative of Heterotardigrada. These new analyses allow us to phylogenetically reconstruct important features of genome evolution in Tardigrada. We use available data from tardigrades to interrogate several recent models of body plan evolution in Panarthropoda. Although anterior segments of panarthropods are highly diverse in terms of anatomy and development, both within individuals and between species, we conclude that a simple one-to-one alignment of anterior segments across Panarthropoda is the best available model of segmental homology. In addition to providing important insight into body plan diversification within Panarthropoda, we speculate that studies of tardigrades may reveal generalizable pathways to miniaturization.

Animals↗