Search Results (94)

The Zona Pellucida (ZP) and its structural analogs are evolutionarily ancient extracellular matrix components. These are essential for oocyte protection, species-specific gamete recognition, and prevention of polyspermy across Metazoa. Defined by the conserved ZP-domain—comprising ZP-N and ZP-C subdomains—these glycoproteins self-assemble into fibrillar matrices through tightly regulated polymerization. Mechanisms of the regulated polymerization involve furin cleavage, disulfide bonding, and hydrophobic interactions. Once considered a vertebrate innovation, the canonical ZP-domain—defined by its bipartite ZP-N/ZP-C architecture, eight conserved cysteine residues, and capacity for matrix polymerization—is now recognized as an ancient metazoan extracellular module, with homologs identified in basal lineages including Porifera, Cnidaria, and Placozoa. While ZP-like sequences have been reported in choanoflagellates such as Salpingoeca rosetta, these lack the complete canonical features and are considered distant structural relatives rather than true ZP-modules. There they function in cell adhesion and tissue integrity, suggesting an origin predating the evolution of specialized reproductive coats. Previous phylogenetic analyses across 97 metazoan species have revealed that vertebrate ZP genes arose from ancestral duplications of the canonical ZP-module. Accordingly, they give rise to eight subfamilies (ZP1–ZP4, ZPD, ZPAX, ZPX, ZPY), with lineage-specific expansions, losses, and pseudogenization reflecting adaptations to diverse reproductive strategies. Positive selection in sperm-binding regions of ZP2 and ZP3 drives a rapid adaptive evolution. It underscores coevolutionary arms races with sperm ligands, contributing to reproductive isolation and speciation. In invertebrates such as abalone and insects, ZP-domain proteins mediate analogous functions through lineage-specific elaborations, including tandem repeats and domain shuffling. Post-translational modifications, particularly glycosylation, fine-tune sperm receptor specificity and matrix stability. The functional transition from a general protective barrier in early metazoans to a sophisticated gamete recognition interface in vertebrates exemplifies modular evolution. This synthesis highlights the domain-level deep homology of ZP-domain proteins as a foundational element of metazoan extracellular matrices, repurposed through gene duplication, neofunctionalization, and selection to meet the demands of evolving reproductive modes. These insights bridge evolutionary biology, reproductive medicine, and developmental genetics. However, major gaps remain, including unresolved orthology between vertebrate and invertebrate ZP genes, the relative contribution of glycans versus protein backbone in sperm recognition, and the lack of functional evidence for canonical ZP-domain proteins in insects. Future studies integrating glycoproteomics, single-cell transcriptomics, and CRISPR-based models are needed to resolve these questions. Full article

Background: The Interleukin-6 (IL6)–Interleukin-6 receptor (IL6R)–Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling pathway plays a crucial role in innate immunity by inducing the production of various immune effectors. However, its stepwise evolutionary assembly across metazoans remains incompletely characterized. Methods: This study systematically screened 18 metazoan phyla or subphyla for the presence of IL6 family cytokines, their receptors, JAKs, and STATs. Phylogenetic relationships were constructed using Neighbor-Joining methods, and domain architectures were predicted via SMART. Results: IL6 was found only in vertebrates, whereas IL6R could be traced to Mollusca. JAK and STAT appeared early in Porifera. IL6R, JAK1/2, STAT1 and STAT5A/B first co-existed in Mollusca. The IL-6 co-receptor gp130 was detected in fish, but was not reliably detected in available reptiles’ and birds’ genomes. Conclusions: The IL6-IL6R-JAK-STAT pathway was assembled incrementally: JAK and STAT were first detected in Porifera, IL6R was added in Mollusca to form the IL6R-JAK-STAT module, and finally, most IL6 family cytokines were present in vertebrates (fish). These findings might provide a pre-existing molecular framework that facilitated the subsequent evolution of the complete pathway in vertebrates. Collectively, this study provides a comprehensive evolutionary framework for the stepwise assembly of the IL6-IL6R-JAK-STAT signaling pathway across metazoans. Full article

Background: Isotomidae is one of the most common Collembola families, comprising 1484 species belonging to four subfamilies: Isotominae, Proisotominae, Anurophorinae, and Pachyotominae, while the subfamilial classification remains contentious and lack of molecular phylogenetic evidence. Methods: We sequenced and assembled the mitochondrial genomes (mitogenomes) of three species (Parisotoma sp., Folsomia sp. 1, and Folsomia sp. 2. Combining these with 10 mitogenomes available from GenBank, we reconstructed the phylogeny of Isotomidae based on a dataset of 13 species representing all four subfamilies. Results: These new mitogenomes, with lengths of 15,741 bp, 16,295 bp, and 16,765 bp, respectively, exhibit the typical metazoan gene set (13 PCGs, 22 tRNAs, 2 rRNAs) and show high structural conservation with other Collembola species. However, phylogenetic analyses based on concatenated protein-coding genes revealed significant incongruence with traditional classification. While Isotomidae was recovered as monophyletic, both Isotominae and Anurophorinae were recovered as paraphyletic. Specifically, Parisotoma sp. formed a distinct lineage closer to the derived subfamilies than to the core Isotominae, and the representative of Pachyotominae (Paranurophorus simplex) was recovered nested within Anurophorinae, suggesting potential subfamilial misclassification or paraphyly. Furthermore, Proisotoma minuta was identified as an independent sister lineage to the Anurophorinae + Pachyotominae clade. Conclusions: Our findings suggest that the current subfamily boundaries are not natural and that key diagnostic traits, such as furcal structure, likely reflect symplesiomorphies or various forms of homoplasy-including convergent evolution, parallelism, and evolutionary reversals—rather than unique synapomorphies defining monophyletic groups. This study provides essential genomic resources and highlights the need for an integrative taxonomic revision of Isotomidae that incorporates both molecular and morphological data, with particular emphasis on redefining subfamilies boundaries and reassessing diagnostic morphological traits. Full article

Tarantulas (family Theraphosidae) are ecologically significant invertebrate predators in terrestrial ecosystems, but many species face threats from habitat fragmentation and unsustainable collection for the international pet trade. Brachypelma albiceps, a CITES Appendix II-listed species, lacks comprehensive mitochondrial genome characterization, limiting phylogenetic and evolutionary studies. Here, we report a complete mitochondrial genome sequence for B. albiceps (13,856 bp; GC content 32.84%) and provide detailed annotation. The genome exhibits typical metazoan mitochondrial organization, containing 13 protein-coding genes (PCGs), 22 tRNAs, and 2 rRNAs, with an AT-rich nucleotide composition (67.16%) characteristic of arthropod mitochondria. Comparative analyses of B. albiceps and six other Mygalomorphae species revealed strong biases toward A/T-ending codons and avoidance of G/C-ending codons. ENC–GC3s, neutrality, and PR2 analyses consistently indicate that natural selection plays a dominant role in shaping synonymous codon usage, with mutation pressure also contributing. Phylogenetic reconstruction based on 10 high-quality mitochondrial protein-coding genes from 23 spider species confirmed the placement of B. albiceps within the family Theraphosidae and its close phylogenetic relationship to Cyriopagopus species. These results provide valuable genomic resources for the Theraphosidae systematics, enhance our understanding of codon bias evolution, and provide critical DNA barcode data for forensic identification of CITES-regulated specimens in the illegal wildlife trade. Full article

Mitochondria play essential roles for animal reproduction, influencing not only cellular energetics but also gamete quality, inheritance and evolutionary patterns. Currently, most research still focuses on chordates or mitochondrial diseases and their impact on the health of germ cells. However, few studies focus on integrative synthesis that connect comparative morphology, inheritance mechanisms and evolutionary theory. In this review, we integrate cross-phyla evidence to explore two interconnected dimensions: the fate of mitochondria during gametogenesis and the strategy shaping their evolution. We compare mitochondrial morphology, distribution, and metabolic strategies in gametogenesis, revealing how these traits align with reproductive modes and ecological adaptations. Then we further discuss how mitochondrial genome evolution, bottleneck effects and mito-nuclear coevolution contribute to germline stability and maternal inheritance. Special attention is given to exceptional systems such as Doubly Uniparental Inheritance (DUI) in bivalves, which challenges conventional mode of strictly maternal transmission and illuminates the flexibility of mito-nuclear evolution. Altogether, these perspectives highlight mitochondria as gatekeepers and evolutionary recorders in the reproductive systems across metazoans, providing a unifying framework for future research across ecology, evolution and molecular biology. Full article

To broaden the scope of research on the characteristics and evolutionary relationships within the heat shock protein 70 (Hsp70) family, encompassing its non-canonical members, amino acid sequences of Hsp70-12, Hsp70-13, and Hsp70-14, alongside those of traditional Hsp70, were collected and analyzed. The findings indicate that, during the evolution of metazoans, the various Hsp70 groups diverged from one another. Specifically, Hsp70-12 emerges as the least conserved member, as evidenced by structural alignment data and the Ka/Ks ratio. It not only represents the most distantly related group to traditional Hsp70 but also stands out as the sole alkaline group within the family. In contrast, Hsp70-13 exhibits a close evolutionary relationship with traditional Hsp70, albeit with the notable loss of its C-terminal domain. Hsp70-14 occupies an intermediate position between Hsp70-12 and Hsp70-13. Phylogenetic analysis suggests that these groups diverged prior to the advent of invertebrates. Furthermore, five conserved motifs within the ATP-binding domain of Hsp70, which serve as distinguishing features for Hsp70 groups, were identified. The diverse characters of the non-canonical Hsp70s are probably related to their special cellular location and tissue specificity. Together, the results of this research will help identify and categorize Hsp70s. Further research that aims at identifying additional non-canonical Hsp70 members and elucidating the distinct characteristics and functions of these molecular chaperones will enhance our comprehension of the origin and evolutionary trajectory of the Hsp70 family. Full article

Phylum Cnidaria occupies an early branching position in the evolution of eukaryotes, establishing both close and distant relationships with most other eukaryotic metazoans. Budding encompasses the complete processes of cell proliferation, differentiation, and tissue regeneration, making it an ideal model for exploring various aspects of cellular function and evolution. Additionally, budding serves as the primary reproductive method for increasing the cnidarian population. This asexual reproductive phase is critical for managing and mitigating cnidarian outbreaks. This paper summarizes the common factors influencing budding, the signaling pathways involved and their associated functions, and the methodologies employed in relevant research, providing a theoretical foundation for the prevention and control of cnidarian populations. Full article

The present, brief review paper summarizes previous studies on a new interpretation of the presence and absence of regeneration in invertebrates and vertebrates. Broad regeneration is considered exclusive of aquatic or amphibious animals with larval stages and metamorphosis, where also a patterning process is activated for whole-body regeneration or for epimorphosis. In contrast, terrestrial invertebrates and vertebrates can only repair injury or the loss of body parts through a variable “recovery healing” of tissues, regengrow or scarring. This loss of regeneration likely derives from the change in genomes during land adaptation, which included the elimination of larval stages and intense metamorphosis. The terrestrial conditions are incompatible with the formation of embryonic organs that are necessary for broad regeneration. In fact, no embryonic organ can survive desiccation, intense UV or ROS exposition on land, and rapid reparative processes without embryonic patterning, such as recovery healing and scarring, have replaced broad regeneration in terrestrial species. The loss of regeneration in land animals likely depends on the alteration of developmental gene pathways sustaining regeneration that occurred in progenitor marine animals. Terrestrial larval stages, like those present in insects among arthropods, only metamorphose using small body regions indicated as imaginal disks, a terrestrial adaptation, not from a large restructuring process like in aquatic-related animals. These invertebrates can reform body appendages only during molting, a process indicated as regengrow, not regeneration. Most amniotes only repair injuries through scarring or a variable recovery healing, occasionally through regengrow, the contemporaneous healing in conjunction with somatic growth, forming sometimes new heteromorphic organs. Full article

The Notch signaling pathway plays a major role in embryological development and in the ongoing life processes of many animals. Its role is to provide cell-to-cell communication in which a Sender cell, bearing membrane-embedded ligands, instructs a Receiver cell, bearing membrane-embedded receptors, to adopt one of two available fates. Elucidating the evolution of this pathway is the topic of this paper, which uses an orthologs approach, providing a comprehensive basis for the study. Using BLAST searches, orthologs were identified for all the 49 components of the Notch signaling pathway. The historical time course of integration of these proteins, as the animals evolved, was elucidated. Insofar as cell-to-cell communication is of relevance only in multicellular animals, it is not surprising that the Notch system became functional only with the evolutionary appearance of Metazoa, the first multicellular animals. Porifera contributed a quarter of the Notch pathway proteins, the Cnidaria brought the total to one-half, but the system reached completion only when humans appeared. A literature search elucidated the roles of the Notch system’s components in modern descendants of the ortholog-contributing ancestors. A single protein, the protein tyrosine kinase (PTK) of the protozoan Ministeria vibrans, was identified as a possible pre-Metazoan ancestor of all three of the Notch pathway proteins, DLL, JAG, and NOTCH. A scenario for the evolution of the Notch signaling pathway is presented and described as the co-option of its components, clade by clade, in a repurposing of genes already present in ancestral unicellular organisms. Full article

Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) inflammasomes are multiprotein signaling platforms that control the inflammatory response and coordinate antimicrobial defense. In the present study, the distribution of NLR, Caspase-1, and gasdermin (GSDM) homologues and their structural characteristics and evolutionary relationships were systematically analyzed in metazoa according to the genomes of species. In invertebrates, there were only NLRC and/or NLRD presented from sponge to amphioxus, and according to the evolutionary tree, NLR from sponge located in the most primitive position. Caspase-1 existed in some metazoan phyla (Brachiopoda, Ectoprocta, Arthropoda, Mollusca, Annelia, Nematoda, Platyelminthes, Coelenterate, and Porifera) and its activation sites were relatively conserved. The amino acid sequences and three-dimensional structures of N-terminal CARD/Death domain of NLR and Caspase-1 were similar in species from sponge to human. NLR and Caspase-1 co-existed in species of Brachiopoda, Mollusca, Annelia, Coelenterate, and Porifera. There was only GSDME or PJVK found in some phyla of invertebrates and their cleavage sites were conserved (DxxD). And it was predicted that the NLR inflammasome in inducing pyroptosis could occur in species of Brachiopoda, Mollusca, Annelia, and Coelenterate. These studies indicated that NLR inflammasome emerged early in sponges of metazoa, and NLR inflammasome in inducing pyroptosis first appeared in Coelenterate, suggesting that inflammasome and its mediated pyroptosis had existed in the early stage of metazoa, but they had been lost in many species during evolution. Full article

In mammals, mixed lineage kinase domain-like protein (MLKL) is the executor of necroptosis. MLKL comprises an N-terminal domain (NTD), which alone suffices to trigger necroptosis by forming pores in the plasma membrane, and a C-terminal domain that inhibits the NTD activity. Evolutionarily, MLKL is poorly conserved in animals and not found in Protostomia. Although MLKL orthologs exist in invertebrate Deuterostomia, the biological activity of invertebrate MLKL is unknown. Herein, we examined 34 metazoan phyla and detected MLKL not only in Deuterostomia but also in Protostomia (Rotifera). The Rotifera MLKL exhibited low identities with non-Rotifera MLKL but shared relatively high identities with non-metazoan MLKL. In invertebrates, MLKL formed two phylogenetic clades, one of which was represented by Rotifera. In vertebrates, MLKL expression was tissue-specific and generally rich in immune organs. When expressed in human cells, the MLKL-NTD of Rotifera, Echinodermata, Urochordata, and Cephalochordata induced strong necroptosis. The necroptotic activity of Rotifera MLKL depended on a number of conserved residues. Together these findings provided new insights into the evolution of MLKL in Metazoa and revealed the biological activity of invertebrate MLKL. Full article

From the late Carboniferous to the early Permian, multiple pulses of glaciation and deglaciation have been caused by the LPIA. The Pennsylvanian period experienced phases of recovery, proliferation, and decline, ultimately forming a reef system distinctly different from that of the Mississippian period. During the late Bashkirian to Moscovian, the metazoan reef experienced a limited resurgence, with reef predominantly formed by chaetetid developing in the United States, northern China, and Japan. During the Kasimovian to Gzhelian, the phylloid algal reef dominated the global reef systems. In the late Pennsylvanian, bioconstruction cases and paleoenvironmental proxies in southern Guizhou Province were studied to investigate the composition, recovery, and evolutionary processes of the bioconstructions as well as their response to environmental variations during this period. Several bioconstructions have been reported in the Lumazhai section of Houchang Town, Guizhou Province, southern China, from the Moscovian to the Gzhelian. The upper Carboniferous strata are well-preserved and continuously exposed. The continuous strata, abundant fossils, and diverse bioconstructions provide excellent research materials for exploring the mutual constraints between organisms and their environment. This study identified ten microfacies, whose vertical evolution indicated significant changes in the depositional environment related to relative sea-level fluctuations. Skeletal grains are widely present in these facies. Among them, foraminifera, algae, bryozoans, crinoids, and Tubiphytes are the most common and exhibit distinct distribution characteristics in various environments. Quantitative statistics, CCA and theoretical ecospace have been utilized to examine and interpret environmental impact factors. Quantitative analysis of their relative abundance and distribution patterns provides insights into the complex interactions between organisms and environmental factors. The relative abundances of different organisms and factors controlling their bioconstructions are influenced by relative sea-level changes. CCA analysis reveal that hydrodynamic conditions are the primary influencing factor. Variation trends in average tiering and motility reveal the characteristics of biological communities during environmental changes in phylloid algae and microbial bioconstructions. These bioconstructions are not directly correlated with changes in environmental factors, and the biological communities in phylloid algae mounds and biostromes exhibit similar organism compositions and ecological niches across different environments. Full article

Cnidarians are among the most important diploblastic organisms, elucidating many of the early stages of Metazoan evolution. However, Cnidarian fossils from Cambrian deposits have been rarely documented, mainly due to difficulties in identifying early Cnidarian representatives. Halysites, a tabulate coral from Silurian reef systems, serves as a crucial taxon for interpreting Cambrian cnidarians. Traditionally, the biological characteristics of Halysites have been analyzed using methods limited by pretreatment requirements (destructive testing) and the chamber size capacity of relevant analytical instruments. These constraints often lead to irreversible information loss and inadequate data extraction. This means that, to date, there has been no high-resolution three-dimensional mineralization analysis of Halysites. This study aims to introduce novel, non-destructive techniques to analyze the internal structure and chemical composition of Halysites. Furthermore, it seeks to elucidate the relationship between coral organisms and biomineralization in reef settings and to compare Silurian Tabulata with putative Cambrian cnidarians. Techniques such as micro-X-ray fluorescence spectrometry (micro-XRF), micro-X-ray computed tomography (micro-CT), and scanning electron microscopy (SEM) were employed in this research. With the help of high-resolution micro-CT scanning, we identify the growth pattern of Halysites, showing both lateral and vertical development. The lateral multiple-branching growth pattern of Halysites corals is first established herein. The flaggy corallite at the initial stage of branching is also observed. The micro-XRF mapping results reveal the occurrence of septa spines for Halysites, a trait previously thought rare or absent. Additionally, the ratio of coral volume to the surrounding rock was assessed, revealing that Halysites reefs were relatively sparse (volume ratio = ~30%). The cavities between Halysites likely provided more space for other organisms (e.g., rugose corals and bryozoans) when compared to other coral reef types. Additionally, we provide a comparative analysis of post-Cambrian colonial calcareous skeletons, offering insights into the structural features and growth patterns of early skeletal metazoans across the Ediacaran–Cambrian boundary. Full article

Ubiquitination is an evolutionary, ancient system of post-translational modification of proteins that occurs through a cascade involving ubiquitin activation, transfer, and conjugation. The maturation of this system has followed two main pathways. The first is the conservation of a universal structural fold of ubiquitin and ubiquitin-like proteins, which are present in both Archaea and Bacteria, as well as in multicellular Eukaryotes. The second is the rise of the complexity of the superfamily of ligases, which conjugate ubiquitin-like proteins to substrates, in terms of an increase in the number of enzyme variants, greater variation in structural organization, and the diversification of their catalytic domains. Here, we examine the diversity of the ubiquitination system among different organisms, assessing the variety and conservation of the key domains of the ubiquitination enzymes and ubiquitin itself. Our data show that E2 ubiquitin-conjugating enzymes of metazoan phyla are highly conservative, whereas the homology of E3 ubiquitin ligases with human orthologues gradually decreases depending on “molecular clock” timing and evolutionary distance. Surprisingly, Chordata and Echinodermata, which diverged over 0.5 billion years ago during the Cambrian explosion, share almost the same homology with humans in the amino acid sequences of E3 ligases but not in their adaptor proteins. These observations may suggest that, firstly, the E2 superfamily already existed in its current form in the last common metazoan ancestor and was generally not affected by purifying selection in metazoans. Secondly, it may indicate convergent evolution of the ubiquitination system and highlight E3 adaptor proteins as the “upper deck” of the ubiquitination system, which plays a crucial role in chordate evolution. Full article

Inosine is a nucleotide resulting from the deamination of adenosine in RNA. This chemical modification process, known as RNA editing, is typically mediated by a family of double-stranded RNA binding proteins named Adenosine Deaminase Acting on dsRNA (ADAR). While the presence of ADAR orthologs has been traced throughout the evolution of metazoans, the existence and extension of RNA editing have been characterized in a more limited number of animals so far. Undoubtedly, ADAR-mediated RNA editing plays a vital role in physiology, organismal development and disease, making the understanding of the evolutionary conservation of this phenomenon pivotal to a deep characterization of relevant biological processes. However, the lack of direct high-throughput methods to reveal RNA modifications at single nucleotide resolution limited an extended investigation of RNA editing. Nowadays, these methods have been developed, and appropriate bioinformatic pipelines are required to fully exploit this data, which can complement existing approaches to detect ADAR editing. Here, we review the current literature on the “bioinformatics for inosine” subject and we discuss future research avenues in the field. Full article