Search Results (94)

Ribose 2′-O-methylation (Nm), a key RNA modification, is catalyzed by diverse 2′-O-methyltransferases (2′-O-MTases), yet the evolutionary trajectories of these enzymes remain poorly studied. Here, with a comprehensive collection of functionally validated 2′-O-MTases, we classified them into 11 families based on the distinct methyltransferase (MTase) domains. Homology searches across 198 species identified 6746 proteins, revealing the widespread distribution of 2′-O-MTases across the Tree of Life. Eight MTase domains (e.g., FtsJ, SpoU-methylase) existed both in eukaryotes and prokaryotes, indicating their ancient origin in the Last Universal Common Ancestor (LUCA). In contrast, the AdoMet-MTase, TRM13, and Trm56 domains are lineage-specific. Copy number expansion of most 2′-O-MTase families occurred as life evolved from prokaryotes to eukaryotes, where they might engage in more complex regulation of cell differentiation and development. Domain composition, Ka/Ks ratio, and domain structural analyses showed that purifying selection conserved catalytic domains across most families, despite the frequent integration of auxiliary domains. Notably, the FtsJ family diverged into three deeply separated lineages via remodeling the catalytic pocket, with each lineage specializing in the methylation of mRNA caps, rRNA, or tRNA. These findings illuminate the evolutionary trajectory of 2′-O-MTases, highlighting their ancient multiple origins and functional diversification. Full article

Mammalian renal intercalated cells are known for their role in acid secretion and maintaining acid–base balance. Herein, we discuss the theoretical reasons behind their development based on published data, focusing on the unique characteristics of renal intercalated cell biology that distinguish them from other mammalian cell types, while simultaneously attempting to explain the persistence of cells similar to intercalated cells throughout evolution. In addition, we traced these characteristics phylogenetically back to the simplest organisms. Intercalated cells have several functions and attributes. First, they contribute to kidney defense mechanisms in response to both infectious and non-infectious kidney damage. Second, intercalated cells are energized by V-ATPases in a manner similar to that of protozoa. Third, they possess T-antigens, which are commonly found in embryonic and cancer cells and which confer invasive abilities to these cells. Fourth, their plasticity enables the regeneration of other epithelial cells. These observations indicate that the origins of renal intercalated cells may be traceable back to amoeboid cells that originated from an evolutionary lineage including protists, or even to the last eukaryote common ancestor. The theoretical framework presented herein supports two predictions: first, that sponge amoebocytes possess membrane V-ATPase and are sensitive to bafilomycin, but not to ouabain; and second, that sponge amoebocytes—along with cells from diploblasts (such as Xenacoelomorpha), cnidarians, worms, fish and mollusk ionocytes, and the entire cell lineage containing V-ATPase, carbonic anhydrase, and anion exchangers (HCO₃⁻/Cl⁻)—have innate immunity, cellular dedifferentiation, and regeneration capabilities. Full article

Botiidae is a small family of freshwater fishes distributed across Southeast Asia, South Asia, and East Asia. It comprises two subfamilies: the diploid Leptobotiinae and the tetraploid Botiinae. Whether species in the Botiinae are autotetraploids or allotetraploids and how many polyploidization events occurred during the evolution of this subfamily remain open questions. The phylogenetic relationships and biogeography of the Botiidae also require further investigation. In the current study, we compared phylogenetic trees constructed using DNA sequences from the mitochondrial genome and five phased nuclear genes. We also performed whole genome sequencing for two tetraploid species: Chromobotia macracanthus and Yasuhikotakia modesta. Genome profiling of five botiine species suggests that they are likely of allotetraploid origin. Nuclear gene tree topologies indicate that the tetraploidization of the Botiinae occurred only once in the common ancestor of this subfamily. Although the possible maternal progenitor and paternal progenitor of the Botiinae cannot be determined, the subfamily Leptobotiinae can be excluded as a progenitor. The gene trees built in this study generally agree on the following sister group relationships: Leptobotiinae/Botiinae, Leptobotia/Parabotia, Chromobotia/Botia, Yasuhikotakia/Syncrossus, and Sinibotia/Ambastaia. Clades formed by the last two generic pairs are also sisters to each other. Timetree analyses and ancestral range reconstruction suggest that the family Botiidae might have originated in East Asia and Mainland Southeast Asia approximately 51 million years ago and later dispersed to South Asia and the islands of Southeast Asia. Full article

Metabolism, the network of biochemical reactions that powers life, arose under conditions radically different from those on Earth today. Investigating its origins reveals how initially simple chemical processes gradually integrated nucleic acid and then protein catalysts, becoming progressively more complex and regulated until they evolved into the enzyme-rich systems observed in modern organisms. Here, we integrate multiple perspectives on the origin of metabolism, focusing primarily on an evolutionary trajectory from an RNA-based world, where ribozymes, metal ions, coenzymes, small peptides, and other small organic molecules worked in concert, to enzyme-driven metabolic networks. We also address the longstanding debates on whether these early metabolic pathways were largely autotrophic or heterotrophic, and consider so-called “pre-metabolisms” (non-enzymatic networks) as an alternative conceptual framework. We discuss key examples such as the Wood–Ljungdahl (W–L) pathway and the reverse tricarboxylic acid (TCA) cycle, both posited to function under early Earth conditions. Finally, we examine how the environment (e.g., minerals, clays, hydrothermal vents) shaped early metabolism, describe unresolved questions about the Last Common Ancestor’s catalytic repertoire and propose future directions that link geochemical insights with molecular biology and synthetic approaches. Full article

Mammalian glutamate dehydrogenase (GDH) is an indispensable metabolic enzyme. GDH duplication has led to the presence of two paralogs, GDH1 and GDH2, in apes. Multiple GDH pseudogenes are also present in the human genome. The novel GDH2, supposed to be a target of positive selection, differs from GDH1 in regulation and is believed to be tightly linked to brain development. Although the differences of modern human GDH2 from GDH2 of other apes have been studied, the evolution of ancient human GDH2 remains a blank space. The goal of this work was to elucidate GDH2 evolution in the genus Homo using the accumulated data on the ancient genomes with high coverage—three Neanderthal and one Denisovan genome. Such analysis clarifies the difference between GDH2 of the last common ancestor of humans and chimpanzees and all Homo to be in M468L substitution, localized in the regulatory “antenna” region of the protein. A few novel missense mutations have been found in Denisovan and Altai Neanderthal GDH2, namely R76H, present in both genomes, and Denisovan-specific T154P, I358L, and S498A substitutions. Another mutation, R352K, has likely occurred independently in modern humans and later Neanderthals. The potential impact of these mutations was estimated using GDH2 structural data and evidence from contemporary medical data. All substitutions are supposed to be benign, with only the S498A GDH2 substitution connected to Parkinson’s disease with late onset. Additionally, the ancient genomes were revealed to have all GDH pseudogenes present in modern humans, including the RNA-coding ones. The GLUD1P3 RNA expression was found to correlate negatively with GDH1 in human tissues. A possible regulatory role has been proposed, and the GLUD1P3 RNA sequence identity in all the studied human genomes suggests its conservation in the genus Homo. Full article

Background: The RSPO gene family encodes secreted glycoproteins that are rich in cysteine, which generally serve as activators of the Wnt signaling pathway in animals. Four types of this family have been identified in a few model species. However, the evolution of the family remains unclear. Methods: In this study, we identified a total of 1496 RSPO homologs through an extensive survey of the RSPO genes in 430 animals. Gene family clustering and phylogenetic analysis identified four major subtypes of the family (RSPO1–RSPO4) and clarified their distribution of copy number in different species. Results and Conclusions: Members of the RSPO4 subfamily that were closest to ancestral forms existed in both Deuterostomes and Protostomates, and we speculate that representatives of this subfamily already existed in Urbilatera, the last common ancestor of Deuterostomes. Particularly, in some RSPO3 subtypes of Actinopterygii (ray-finned fishes), an FU repeated motif with three conserved cysteines was identified. Further conservative analysis of amino acids and alignment of tertiary protein structure revealed the potential functional sites for each subgroup. The results provide insight into the phylogenetic relationships and evolutionary patterns of conserved motifs of RSPO family genes in animal kingdoms, which will guide further studies on the biological functions of RSPO in other non-model species. Full article

Sargassum hemiphyllum var. chinense is a common brown seaweed along the southeastern coast of China, playing a significant ecological role and possessing considerable resource utilization value. However, its genetic diversity and phylogeographic patterns remain poorly understood. In this study, we employed multiple molecular markers, including the nuclear ITS sequence (ribosomal internal transcribed spacer), the plastid rbcL gene (encoding the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase), and the mitochondrial cox3 and cox1 genes (encoding cytochrome c oxidase subunits III and I, respectively), to elucidate the genetic and phylogeographic structure of S. hemiphyllum var. chinense. Our findings demonstrate that the combined use of plastid and mitochondrial gene sequences is suitable for phylogeographic studies of this species. Genetic structure difference was observed among 15 populations which localities covering most of its distribution range, likely resulting from colonization by ancestors of different origins and limited gene flow among populations. The study revealed two distinct lineages of S. hemiphyllum var. chinense, exhibiting a north–south geographical distribution with a mixed zone in the southern Fujian–eastern Guangdong coastal region. These lineages are inferred to have diverged during the Middle to Late Pleistocene due to the isolation of the East China Sea and South China Sea during glacial periods. Sub-lineage differentiation was also detected within the northern lineage. The southern lineage experienced demographic expansion following the end of the Last Glacial Maximum, while the northern lineage remained stable. The southern Fujian–eastern Guangdong region, characterized by high genetic diversity, may have served as a glacial refugium or a contact zone for the post-glacial recolonization of the two lineages. Global warming may lead to range contraction and reduced genetic diversity in this species. The high genetic diversity area should be prioritized for conservation efforts. Overall, these findings provide insights into the genetic structure status and causes of S. hemiphyllum var. chinense and offer a scientific basis for proposing reasonable measures for its resource management. Full article

Background/Objectives: The origin of genes and genetics is the story of the coevolution of translation systems and the genetic code. Remarkably, the history of the origin of life on Earth was inscribed and preserved in the sequences of tRNAs. Methods: Sequence logos demonstrate the patterning of pre-life tRNA sequences. Results: The pre-life type I and type II tRNA sequences are known to the last nucleotide with only a few ambiguities. Type I and type II tRNAs evolved from ligation of three 31 nt minihelices of highly patterned and known sequence followed by closely related 9 nt internal deletion(s) within ligated acceptor stems. The D loop 17 nt core was a truncated UAGCC repeat. The anticodon and T 17 nt stem-loop-stems are homologous sequences with 5 nt stems and 7 nt U-turn loops that were selected in pre-life to resist ribozyme nucleases and to present a 3 nt anticodon with a single wobble position. The 7 nt T loop in tRNA was selected to interact with the D loop at the “elbow”. The 5′-acceptor stem was based on a 7 nt truncated GCG repeat. The 3′-acceptor stem was based on a complementary 7 nt CGC repeat. In pre-life, ACCA-Gly was a primitive adapter molecule ligated to many RNAs, including tRNAs, to synthesize polyglycine. Conclusions: Analysis of sequence logos of tRNAs from an ancient Archaeon substantiates how the pre-life to life transition occurred on Earth. Polyglycine is posited to have aggregated complex molecular assemblies, including minihelices, tRNAs, cooperating molecules, and protocells, leading to the first life on Earth. Full article

The Kunlun, Arjin, and Qilian mountain ranges mark the northern edge of the Qinghai–Tibet Plateau (QTP), where rapid uplift and Quaternary glacial cycles have shaped a unique cold desert ecosystem and species distribution. Despite sampling challenges, phylogeographic studies are crucial for understanding reptile populations such as the Qinghai toad-headed agama (Phrynocephalus vlangalii), a viviparous lizard with limited dispersal and multiple subspecies in the northeastern QTP. Our fieldwork identified populations of P. vlangalii on the northern slope of the Kunlun–Arjin Mountains, similar to the controversial subspecies P. v. lidskii. We analyzed 130 individuals from the northern slope of the Kunlun–Arjin–Qilian Mountains and 253 individuals from GenBank, using three mitochondrial genes and two nuclear genes to assess intraspecific differentiation and demographic history. We found high haplotype diversity and low nucleotide diversity in P. vlangalii, with phylogenetic analyses revealing six distinct clades. Clade VI, confirmed as P. v. lidskii, and Clade IV, a new genetic lineage, were identified alongside three recognized subspecies. Genetic variation was largely attributed to clade splitting, indicating significant divergence. The Mantel test indicated that geographical and environmental factors drove population differentiation. Bayesian molecular clock analysis suggested that the most recent common ancestor of P. vlangalii lived 2.55 million years ago, influenced by the Qinghai–Tibet Movement and glacial cycles. Demographic history and ecological niche modeling (ENM) indicated no population decline during the Last Glacial Maximum, supporting the glacial maximum expansion model, with ENM predicting future habitat expansion for P. vlangalii. In addition, morphological data from 13 meristic and 15 metric characters confirmed clade differences. Our findings significantly advance our understanding of P. vlangalii diversification, population dynamics and response to geological and climatic changes in the QTP. Full article

Carl Woese’s thesis of cellular evolution emphasized that the last universal common/cellular ancestor (LUCA) must have evolved by drawing from “global inventions”. Yet, existing theories regarding the origin(s) of LUCA have mostly centered upon scenarios that LUCA had evolved mostly independently. In an earlier paper, we advanced a new theory regarding the origin(s) of LUCA that extends Woese’s original insights. Our theory centers upon the possibility that different vesicles and protocells can merge with and acquire each other as a form of variation, selection, and retention, driven by wet-and-dry cycles and other similar cyclical processes. In this paper, we use computer simulation to show that under a variety of simulated conditions, LUCA can indeed be produced by our proposed processes. We hope that our study can stimulate laboratory testing of some key hypotheses that vesicles’ absorption, acquisition, and merger has indeed been a central force in driving the evolution of LUCA. Full article

We propose a hypothesis for the simultaneous emergence of bacteria, archaea, viruses, and mobile elements by sequential and concrete biochemical pathways. The emergence process can be considered analogous to crystallization, where genetic and biochemical systems stabilize as organisms evolve from their common ancestor, the LUCA, which was a non-free-living pool of single operon type genomes including double-stranded (ds) DNA at an ancient submarine alkaline vent. Each dsDNA operon was transcribed by different systems in σ, TFIIB, or TBP genomes. Double-stranded DNA operons can fuse and stabilize through the action of specific transcription systems, leading to differentiation between the Bacteria (σ genome) and Archaea (TBP genome) domains. Error catastrophe can be overcome by the parallel gain of DNA replication and DNA repair mechanisms in both genomes. Enlarged DNA enabled efficient local biochemical reactions. Both genomes independently recruited lipids to facilitate reactions by forming coacervates at the chamber of the vent. Bilayer lipid membrane formation, proto-cell formation with a permeable membrane, proto-cell division, and the evolution of membrane-associated biochemistry are presented in detail. Simultaneous crystallization of systems in non-free-living bacteria and non-free-living archaea triggered the co-crystallization of primitive viruses and mobile elements. An arms race between non-free-living cells and primitive viruses finally led to free-living cells with a cell wall and mature viruses. Full article

Australian elapid snake venoms are uniquely procoagulant, utilizing blood clotting enzyme Factor Xa (FXa) as a toxin, which evolved as a basal trait in this clade. The subsequent recruitment of Factor Va (FVa) as a toxin occurred in the last common ancestor of taipans (Oxyuranus species) and brown snakes (Pseudonaja species). Factor II (prothrombin) activation has been stated as the primary mechanism for the lethal coagulopathy, but this hypothesis has never been tested. The additional activation of Factor VII (FVII) by Oxyuranus/Pseudonaja venoms has historically been considered as a minor, unimportant novelty. This study aimed to investigate the significance of toxic FVII activation relative to prothrombin activation by testing a wide taxonomical range of Australian elapid species with procoagulant venoms. The activation of FVII or prothrombin, with and without the Factor Va as a cofactor, was assessed, along with the structural changes involved in these processes. All procoagulant species could activate FVII, establishing this as a basal trait. In contrast, only some lineages could activate prothrombin, indicating that this is a derived trait. For species able to activate both zymogens, Factor VII was consistently more strongly activated than prothrombin. FVa was revealed as an essential cofactor for FVII activation, a mechanism previously undocumented. Species lacking FVa in their venom utilized endogenous plasma FVa to exert this activity. The ability of the human FXa:FVa complex to activate FVII was also revealed as a new feedback loop in the endogenous clotting cascade. Toxin sequence analyses identified structural changes essential for the derived trait of prothrombin activation. This study presents a paradigm shift in understanding how elapid venoms activate coagulation factors, highlighting the critical role of FVII activation in the pathophysiological effects upon the coagulation cascade produced by Australian elapid snake venoms. It also documented the novel use of Factor Va as a cofactor for FVII activation for both venom and endogenous forms of FXa. These findings are crucial for developing better antivenoms and treatments for snakebite victims and have broader implications for drug design and the treatment of coagulation disorders. The research also advances the evolutionary biology knowledge of snake venoms. Full article

From the most ancient RNAs, which followed an RNY pattern and folded into small hairpins, modern RNA molecules evolved by two different pathways, dubbed Extended Genetic Code 1 and 2, finally conforming to the current standard genetic code. Herein, we describe the evolutionary path of the RNAome based on these evolutionary routes. In general, all the RNA molecules analysed contain portions encoded by both genetic codes, but crucial features seem to be better recovered by Extended 2 triplets. In particular, the whole Peptidyl Transferase Centre, anti-Shine–Dalgarno motif, and a characteristic quadruplet of the RNA moiety of RNAse-P are clearly unveiled. Differences between bacteria and archaea are also detected; in most cases, the biological sequences are more stable than their controls. We then describe an evolutionary trajectory of the RNAome formation, based on two complementary evolutionary routes: one leading to the formation of essentials, while the other complemented the molecules, with the cooperative assembly of their constituents giving rise to modern RNAs. Full article

The complex and diverse phenomenon of fungal bioluminescence has captured human curiosity. Nevertheless, in the field of studies, there are not many attempts made particularly to reveal the new species of these interesting fungi. This study comprehensively reviews the diversity, distribution, evolution, bioluminescence mechanisms, ecological roles, and potential applications of these fungi. Most importantly, we also present an updated list of the reported bioluminescent fungi (122) so far identified from five distinct evolutionary lineages worldwide—Armillaria, Eoscyphella, Lucentipes, Mycenoid, and Omphalotus—mainly in tropical and subtropical areas. Bioluminescent fungi are descended from the last common ancestor of the Mycenoid and the Marasmioid clades of Agaricales, which have been maintained for at least 160 million years of evolution. We underscore the potential for future research to understand the ecological role of bioluminescent fungi, inspiring hope and optimism for the future of this field. 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