Journal of Molecular Evolution最新文献

{"title":"Cystathionine Gamma-Lyase: A Potential Longevity Gene Under Selection?","authors":"Gary J Ren, Frances E Hauser, Elissa Khodikian, Nathan R Lovejoy, Cosima S Porteus","doi":"10.1007/s00239-025-10273-5","DOIUrl":"https://doi.org/10.1007/s00239-025-10273-5","url":null,"abstract":"<p><p>Hydrogen sulfide (H₂S) plays a crucial role in various physiological processes and has been implicated in modulating aging through its impacts on oxidative stress and cellular health. This study investigates the evolutionary dynamics of the cystathionine-β-synthase (CBS), the cystathionine-ƴ-lyase (CSE), and the 3-mercaptopyruvate sulfurtransferase (3-MST) genes, involved in endogenous H₂S production. We investigated CBS, CSE, and 3-MST in long-lived mammals, focusing on the naked mole-rat (Heterocephalus glaber). We hypothesized that these genes would exhibit signs of positive selection linked to extended lifespan. Codon-based evolutionary models were used to compare these genes across 114 mammalian species. Our results revealed a relaxation of purifying selection instead of positive selection in CSE, but not CBS and 3-MST, in long-lived mammals, suggesting an accumulation of mutations that enhance physiological functions related to longevity. In the naked mole-rat, CSE exhibited clear signs of positive selection, particularly in residues G116A and T118V, associated with increased protein stability and enhanced binding affinity to the cofactor pyridoxal-5'-phosphate (PLP). These mutations possibly improve CSE catalytic efficiency and potentially H₂S production, supporting the naked mole-rat's unique adaptations to its subterranean habitat and contributing to its remarkable lifespan. Our findings indicate a potential correlation between longevity and selection on the CSE gene, but not the CBS and 3-MST genes, highlighting the complex role of H₂S in aging and cellular health. The study provides new insights into the molecular mechanisms underlying lifespan extension in long-lived mammals and underscores the potential adaptive significance of H₂S biogenesis in the naked mole-rat.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OrthoXML-Tools: A Toolkit for Manipulating OrthoXML Files for Orthology Data.","authors":"Ali Yazdizadeh Kharrazi, Adrian M Altenhoff, Nikolai Romashchenko, Christophe Dessimoz, Sina Majidian","doi":"10.1007/s00239-025-10271-7","DOIUrl":"https://doi.org/10.1007/s00239-025-10271-7","url":null,"abstract":"<p><p>The OrthoXML file is a standard file format for orthology data. It provides a standardized structure for describing orthologous and paralogous relationships while allowing the user to store custom and database-specific data in the same format. Although many orthology databases use it as a way to export data, there is no comprehensive toolkit for working with this format. Here, we introduce the OrthoXML-tools ( https://github.com/DessimozLab/orthoxml-tools ), a comprehensive toolkit for loading, manipulating, and exporting the OrthoXML files to other formats. We show its capabilities and performance on our benchmarks.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NCBI Orthologs: Public Resource and Scalable Method for Computing High-Precision Orthologs Across Eukaryotic Genomes.","authors":"Dong-Ha Oh, Alexander Astashyn, Barbara Robbertse, Nuala A O'leary, W Ray Anderson, Laurie Breen, Eric Cox, Olga Ermolaeva, Robert Falk, Vichet Hem, J Bradley Holmes, Patrick Masterson, Kelly M McGarvey, Eyal Mozes, John P Torcivia, Mirian T N Tsuchiya, Craig Wallin, Françoise Thibaud-Nissen, Terence D Murphy, Vamsi K Kodali","doi":"10.1007/s00239-025-10268-2","DOIUrl":"https://doi.org/10.1007/s00239-025-10268-2","url":null,"abstract":"<p><p>Orthologs are fundamental for enabling comparative genomics analyses that further our understanding of eukaryotic biology. The unprecedented increase in the availability of high-quality eukaryotic genomes necessitates scalable and accurate methods for orthology inference. The National Center for Biotechnology Information (NCBI) developed \"NCBI Orthologs\", a resource and a computational pipeline designed to meet this challenge within the NCBI RefSeq framework. This system integrates protein similarity, nucleotide alignment, and microsynteny to achieve high-precision ortholog assignments across diverse eukaryotes. The pipeline leverages high-quality RefSeq annotations and processes genomes individually, ensuring scalability. Resulting ortholog data, organized into gene-level anchored sets, enables propagation of functional annotation information and facilitates comparative genomics. Critically, these data are integrated into the NCBI Gene resource, providing users with access from various entry points. The NCBI Datasets resource provides an intuitive interface to explore orthologous relationships on the web and allows bulk data download via the web, command-line tools, and an API. We detail the methodology, including anchor species selection and the decision tree used to arrive at high-confidence one-to-one orthology relationships. NCBI Orthologs is a valuable resource for facilitating functional annotation efforts and enhancing our understanding of eukaryotic gene evolution.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-evolution of alpha-helical transmembrane protein residues: large-scale variant profiling and complete mutational landscape of 2277 known PDB entries representing 504 unique human protein sequences.","authors":"Taner Karagöl, Alper Karagöl, Shuguang Zhang","doi":"10.1007/s00239-025-10262-8","DOIUrl":"https://doi.org/10.1007/s00239-025-10262-8","url":null,"abstract":"<p><p>Membrane proteins play fundamental roles in cellular function, yet the evolutionary dynamics of their amino acid composition remain poorly understood. Our current study investigates the substitutional landscape and evolutionary patterns of hydrophilic and hydrophobic residues in membrane α-helical proteins, addressing a significant gap in our knowledge of protein evolution. We analyzed 2277 high-resolution protein structures from the RCSB Protein Data Bank corresponding to 458 unique PDB structures, 504 UniProt transmembrane entries and their AlphaMissense predicted mutational libraries including more than 5.8 million amino acid substitutions, focusing on known transmembrane α-helical proteins in Homo sapiens. Our analysis showed that the pathological outcome of the substitutions is diverse, as nonpolar to polar changes showed higher pathological scores in general. Notably, F <=> Y substitutions showed significantly lower pathological scores. Our further analysis revealed a significant asymmetry in the evolutionary frequencies of polar and nonpolar amino acids. We identified key residue pairs driving this asymmetry, with F <=> Y, A <=> T, V <=> T and A <=> S co-evolution diverging from the expected negative correlations (Spearman's rho > 0.20, p < 0.001). The V <=> T substitution via an alanine intermediate and the G <=> N substitution via a serine intermediate lower their statistical barrier, which would otherwise require two sequential base changes. We propose two evolutionary game theory (EGT) based models to explain their diversification, with partial correlation analysis on residue frequencies in homolog sequences. These mathematical insights suggest a previously unrecognized evolutionary pressure, potentially linked to functional diversification, which could be targeted to combat drug resistance. Our results offer insights into membrane protein evolution and may inform improved methods for protein structure prediction and design.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of a Novel Human Protein, ORF3, Encoded by Spacer rDNA.","authors":"Yaohui Chen, Jung-Hyun Kim, Hee-Sheung Lee, Sergey Koren, Vladimir Larionov, Adam M Phillippy, David Schlessinger, Ramaiah Nagaraja","doi":"10.1007/s00239-025-10269-1","DOIUrl":"https://doi.org/10.1007/s00239-025-10269-1","url":null,"abstract":"<p><p>An open reading frame in the intergenic spacer of human ribosomal (r)DNA codes for a 190 amino acid, 22 kDa protein that we have named ORF3. It comprises a 5'AluSx repeat sequence encoding 96 amino acids followed by a stretch of 94 amino acids containing a unique repeated stretch of 5 hydrophobic residues. Full copies of ORF3 have been isolated as transformation-associated recombination clones from mouse:human hybrid cell lines containing human chromosomes 21 or 22. In initial instances where the chromosome complement of rDNA repeats is fully resolved in whole genomes, in CHM13 cells, complete copies of ORF3 are mainly concentrated in a tandem cluster on chromosome 21, while other chromosomes contain 1 or 2 full copies, with the sequence in other rDNA repeats interrupted by a frameshift mutation. A diploid cell complement (HG002) again has both complete open reading frames (ORFs) and other copies with the frameshift or deletions. In searches among non-human primate sequences to assess the evolutionary history of ORF3, a > 93% conserved copy of the full sequence of the ORF, as well as copies with in-frame deletions, was found in bonobo, but only fragments homologous to the ORF were seen in chimpanzee, orangutan, and gorilla rDNA examined thus far. ORF3 was expressed as a V5-tagged chimeric protein in human kidney epithelial HEK293 cells, and both ORF3-V5 and endogenous ORF3 were detected with a newly generated antibody. The protein is found in both cytoplasm and nucleus. However, upon treatment of cells with RNase A, the protein is excluded from the nucleus, suggesting that it is in complexes with RNA. Although any function is currently unknown, the ORF3 protein is upregulated, speculatively associated with changes in chromatin, in viral-transformed HEK293 cells and in human diploid fibroblast cells rendered senescent by treatment with etoposide, ionizing radiation, or an oxidant (H₂O₂).</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fascination with RNA Editing: In the Lights of Evolution and Biology.","authors":"Ziyi Wang, Yuange Duan","doi":"10.1007/s00239-025-10270-8","DOIUrl":"https://doi.org/10.1007/s00239-025-10270-8","url":null,"abstract":"<p><p>Adenosine-to-inosine RNA editing is a widespread RNA modification that recodes genetic information and expands proteomic diversity. Exploring its evolutionary and adaptive roles requires multi-dimensional analysis, from sequence conservation to functional impact. In this article, we highlight RNA editing as a fascinating bridge between molecular biology and evolutionary theory-two domains used to be treated separately. Remarkably, RNA editing embodies both diversity (as a consequence of mutation, drift, and selection) and conservation (common ancestor), the two foundational principles of Darwin's theory and modern evolutionary research. While some evolutionary studies emphasize what has changed over time, RNA editing additionally draws attention to conserved signatures that persist across lineages, offering a more integrative perspective on how species evolve while remaining connected through shared molecular ancestry.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Evolutionary History and Functional Significance of the Protein Z-Dependent Protease Inhibitor (ZPI) Across Vertebrates.","authors":"Chennakesavan Suganthi, Parthiban Akshayaa, Tanusree Sengupta, Narayanan Manoj","doi":"10.1007/s00239-025-10267-3","DOIUrl":"https://doi.org/10.1007/s00239-025-10267-3","url":null,"abstract":"<p><p>Serpins, characterized by a conserved structural fold, serve diverse biological roles. Protein Z-dependent protease inhibitor (ZPI), a serpin superfamily member, acts as an endogenous anticoagulant by inhibiting clotting factors Xa (fXa) and XIa (fXIa). Beyond anticoagulation, ZPI has roles in inflammation, cancer, and immune regulation. However, its exact pathophysiological role is yet to be fully characterized. To elucidate ZPI's evolutionary trajectory and non-haemostatic roles, we conducted a comprehensive phylogenetic analysis integrating sequence, gene structure, and synteny data. We identified a lamprey-specific serpin, ZPIL_AGTL_PMA, containing both an inhibitory reactive center loop (RCL) and an angiotensin II (Ang II) motif. This finding suggests that ZPIL_AGTL_PMA represents an ancestral bifunctional serpin from which ZPI and angiotensinogen (AGT), a non-inhibitory serpin involved in blood pressure regulation, evolved by sub-functionalization in jawed vertebrates. This bifunctionality within a single gene in lamprey likely reflects an ancestral vertebrate trait. Gene cluster analyses showed serpinA10 (ZPI) as possibly the earliest member, with other Clade A serpins arising via subsequent duplication. The chromosomal location of this gene cluster is conserved in most vertebrates, except Carnivores and Suidea. Sequence analysis indicated potential non-inhibitory ZPI variants in certain species with atypical non-serine residues at the P1' position within its RCL, a critical determinant of inhibitory serpin activity. The close evolutionary relationship between ZPI and AGT further suggests mechanistic interplay between coagulation and blood pressure regulation, highlighting shared regulatory pathways involving these serpins. Together, these findings expand the functional landscape of ZPI and underscore the dynamic evolution of serpin-mediated physiological processes.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlorophyllide a Oxygenase (CAO) Gene Duplication Across the Viridiplantae.","authors":"Mackenzie C Poirier, Roberta Wright, Marina Cvetkovska","doi":"10.1007/s00239-025-10266-4","DOIUrl":"https://doi.org/10.1007/s00239-025-10266-4","url":null,"abstract":"<p><p>Viridiplantae, a diverse group of green plants and algae that have evolved from a common ancestor, are unified in their ability to produce and use two types of chlorophyll (chlorophyll a and chlorophyll b) to capture light energy. In addition to playing a role in light harvesting, chlorophyll b is required at the appropriate level for the accumulation, assembly, and stability of light-harvesting complexes within the photosynthetic apparatus. Chlorophyll b is synthesized from chlorophyll a by the enzyme chlorophyllide a oxygenase (CAO), a Rieske-type mononuclear non-heme iron oxygenase. A regulatory degron sequence, described in detail only in land plants, regulates the stability of CAO proteins based on the availability of chlorophyll b. Recent identification of CAO gene duplication in bryophyte and green algal species, combined with expanded availability of sequenced genomes within the Viridiplantae, prompted further investigation into the role of gene duplication in the evolution of chlorophyll b biosynthesis. Examination of genomes from 246 plant and algae species revealed independently occurring CAO duplications throughout the Viridiplantae, with a higher prevalence of duplication in land plants compared to their algal relatives. Additionally, we demonstrate that the degron sequence is poorly conserved in chlorophytes, but first appears as a conserved sequence in charophytes, and is very highly conserved among the embryophytes. The evolutionary history and functional role of CAO throughout the Viridiplantae lineage is discussed based on these key observations, adding to our understanding of chlorophyll b biosynthesis and the role of CAO in photosynthetic species.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Codon Usage Evolution in Viruses: Implications for Survival and Pathogenicity.","authors":"Shaikh Kaleem, Ujwal Dahal, Shivani Devi, Bhumandeep Kour, Sharanpreet Kour","doi":"10.1007/s00239-025-10263-7","DOIUrl":"https://doi.org/10.1007/s00239-025-10263-7","url":null,"abstract":"<p><p>Codon usage serves as a fundamental viral signature, influencing survival, adaptation, and pathogenicity. Viruses exhibit distinct codon usage patterns shaped by genome composition, host interactions, and evolutionary pressures. The differences between DNA and RNA viruses in codon usage reflect their replication strategies, host preferences, and genome constraints. Viral adaptation to host codon usage, genome size, and lifestyle further shapes translational efficiency and immune evasion mechanisms. Host tRNA abundance plays a crucial role in viral translation rates, while codon deoptimization is a strategy used by viruses to evade immune detection. Additionally, codon bias is linked to viral virulence, replication rates, and pathogenicity. Building on these concepts, this review synthesizes current knowledge on the interplay between virus-host translational interactions, codon bias-driven viral evolution, and their implications for pathogenesis, immune evasion, and epidemiology, while also outlining their practical applications in vaccine development, antiviral strategies, and viral diagnostics. We discuss current challenges in codon usage studies, including context-dependent variations and limited experimental validation, and propose future research directions that integrate computational and experimental approaches to deepen our understanding of viral codon bias and its role in evolution, host adaptation, and disease control.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for Viruses in Pallas's Long-Tongued Bats (Glossophaga soricina) in Brazil.","authors":"Alexandre Sita, Gabriela E Birlem, Deivid S da Silva, Larissa Mallmann, Meriane Demoliner, Mariana S da Silva, Juliana S Gularte, Vyctoria M A G Pereira, Paula R de Almeida, Alana W Hansen, André A Witt, Juliane D Fleck, Fernando R Spilki, Daniela T da Rocha, Matheus N Weber","doi":"10.1007/s00239-025-10264-6","DOIUrl":"https://doi.org/10.1007/s00239-025-10264-6","url":null,"abstract":"<p><p>Bats are considered a unique group of mammals and are recognized as natural hosts for a variety of emerging viral agents of One Health importance. In Brazil, nine bat families are described, of which the family Phyllostomidae contains the highest number of cataloged species. Within them, the Pallas's long-tongued bat (Glossophaga soricina) is one of the most widely distributed species in South America. G. soricina are specialized in the use of nectar and pollen as food and therefore are extremely important in the dynamics of ecosystems. In this way, the present study aimed to evaluate the presence of viruses from the families Coronaviridae, Paramyxoviridae, Orthomyxoviridae, Reoviridae, and Rhabdoviridae in G. soricina bats. Samples of oral and rectal swabs from 40 bats in four bat colonies were collected in Southern Brazil. Four samples tested positive for coronavirus by PCR. Following DNA sequencing and phylogenetic analyses, they were classified into the Amalacovirus subgenus, within the alphacoronavirus (α-CoV) genus. In addition, it was possible to observe two distinct strains within the same bat colony. The results obtained reinforce that phyllostomids are the main reservoirs of amalacoviruses. Eco-vigilance in bats with close access to urban environments is essential for monitoring possible future spillover events.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}