{"title":"Revisiting Eck and Dayhoff's Building Block Model of Ferredoxin Evolution on Dayhoff's 100th Birthday.","authors":"Gustavo Caetano-Anollés","doi":"10.1007/s00239-025-10283-3","DOIUrl":"10.1007/s00239-025-10283-3","url":null,"abstract":"<p><p>Nearly 60 years ago, Eck and Dayhoff (Science 152:363-366, 1966) aligned amino acids from first and second halves of a ferredoxin sequence, revealing a symmetric CX<sub>2</sub>CX<sub>2</sub>CX<sub>3</sub>CX<sub>18</sub>CX<sub>2</sub>C<sub>2</sub>C<sub>3</sub>C spacing signature in which X<sub>n</sub> denoted intervening residues. This symmetry, along with other cyclic patterns, suggested that a tandem duplication shaped ferredoxin evolution and that the ancestral sequence may have drawn from a reduced amino acid repertoire. Here, I revisit the duplication model using the deep learning-based AlphaFold2 ab initio pipeline, benchmarked against the I-TASSER threading tool. Predicted ancestral structures were obtained with high confidence, with some aligning to the two halves of a reference ferredoxin (PDB entry 1CIF) at acceptable RMSD and TM-score values. A chronology of loops and structural domains further identified which duplicate was ancestral, reinforcing the antiquity of the fold. Loops and domains also dissected the evolution of the [4Fe-4S] ferredoxin superfamily. The resulting structural models provided strong support for the tandem duplication hypothesis and the idea that modular units underpinned early molecular evolution. However, they also challenged the notion that the duplication event arose from a reduced amino acid alphabet. This work revisits Eck and Dayhoff's seminal insights and commemorates Dayhoff's pioneering contributions on the centenary of her birth.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"52-61"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12920312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noreen A Khan, Athira C Rajeev, Althaf Mahin, Athira Perunelly Gopalakrishnan, Prathik Basthikoppa Shivamurthy, Nazah Naurah V, Alimath Sambreena, Rajesh Raju
{"title":"Decoding the Evolution and Co-Phospho-Regulatory Networks of SHROOM Proteins.","authors":"Noreen A Khan, Athira C Rajeev, Althaf Mahin, Athira Perunelly Gopalakrishnan, Prathik Basthikoppa Shivamurthy, Nazah Naurah V, Alimath Sambreena, Rajesh Raju","doi":"10.1007/s00239-025-10300-5","DOIUrl":"10.1007/s00239-025-10300-5","url":null,"abstract":"","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"250-274"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998432","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}
Makarim Elfadil M Osman, Amina I Dirar, Mohanad A Ibrahim, Rieham Sallah H Osman, Doaa Awad Yassin Ali, Somia Elmosharaf Elrayah Yousif, Hana Badreldin Mohamed Abakar, Nada Hassan M Haj, Emadeldin Hassan E Konozy
{"title":"Lectin Gene Families in Three Phaseolus Species: Genome-Wide Identification, Evolutionary Analysis, Pleiotropic Effect, and Regulation Under Multiple Stress Conditions.","authors":"Makarim Elfadil M Osman, Amina I Dirar, Mohanad A Ibrahim, Rieham Sallah H Osman, Doaa Awad Yassin Ali, Somia Elmosharaf Elrayah Yousif, Hana Badreldin Mohamed Abakar, Nada Hassan M Haj, Emadeldin Hassan E Konozy","doi":"10.1007/s00239-025-10278-0","DOIUrl":"10.1007/s00239-025-10278-0","url":null,"abstract":"<p><p>Lectins are a diverse class of proteins that play crucial roles in plant defense, stress responses, and various physiological processes. However, comprehensive comparative analyses of lectin gene families across closely related Phaseolus species are lacking, and the evolutionary and stress-responsive dynamics of these genes remain poorly understood. This study provides a comprehensive genome-wide analysis of lectin genes in three Phaseolus species: P. vulgaris, P. lunatus, and P. acutifolius. Using genomic data from the Phytozome database, we identified 132, 132, and 134 putative lectin genes, respectively, across 8 lectin families, with the legume, GNA, and Nictaba families being the most abundant. Domain architecture analysis revealed a broad structural spectrum, from simple merolectins to complex chimerolectins with multiple domains. Expansion analysis indicated that lectin family expansion primarily occurred through tandem and dispersed duplications with similar syntenic profiles across the Phaseolus species. Codon-based evolutionary models revealed that while most lectin genes are purifying selection, several duplicated pairs from specific families (i.e., legume, Pl-Nictaba, and Pa-Hevein) show site-specific and episodic positive selection, suggesting adaptive divergence linked to functional specialization. Expression profiling under abiotic (salinity, cold) and biotic (bacterial, fungal, insect) stress conditions revealed differential regulation of lectin genes, with multiple genes (14) exhibiting pleiotropic effects through upregulation under several stresses. Regulatory analysis identified transcription factors from AP2, B3, Dof, ERF, MYB, and TCP families as potential upstream regulators of these pleiotropic genes, forming complex cis-regulatory networks integrating environmental and developmental signals. This study provides novel insights into the structural diversity, evolutionary dynamics, and stress-responsive roles of lectins in Phaseolus species and identifies promising targets for improving stress resilience in legume crops.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"28-51"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286369","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":"Transposable Elements Seed Transcription Factor Binding Sites to Sequence-Specific Double-Stranded DNA Binding TF Networks Contributing to Governance of Primate Brain Evolution.","authors":"Gennadi V Glinsky","doi":"10.1007/s00239-025-10285-1","DOIUrl":"10.1007/s00239-025-10285-1","url":null,"abstract":"<p><p>Transposable elements (TEs) have played a pivotal role in shaping the regulatory architecture of mammalian genomes. This contribution reports multiple lines of evidence suggesting that TE have made a significant impact on brain development by providing sequences for thousands of transcription factor binding sites (TFBS). TE-encoded TFBS have scaffolded brain developmental regulatory regions (BDRRs) across mammalian evolution. TFBS density within BDRRs has markedly increased along the evolutionary trajectory from mouse to macaque to chimpanzee, reaching its highest levels in modern humans. This density increase is accompanied by the preferential selection of specific TFs that actually bind genomic regulatory sequences. Consequently, humans and chimpanzees exhibit distinct repertoires of BDRR-bound TFs, which contribute to divergent developmental trajectories across hundreds of brain regions ranging from subcortical to telencephalon structures, including the basal ganglia (12 regions), midbrain (48), thalamus & prethalamus (85), hindbrain & cerebellum (25), limbic system & amygdala (25), neurodevelopmental structures (26). Despite the diversity of sequences contributed by different TEs, they encode TFBS for a relatively small set of ~ 700 TFs that act as central nodes organizing these regulatory landscapes. This provides a unifying framework for understanding both conserved and species-specific patterns of primate brain development. It suggests that TF networks seeded by TEs are key drivers of human neurodevelopmental innovation. Differential enrichment analyses of human vis-à-vis chimpanzee BDRRs identified 25 human BDRR-bound TFs that emanate transcriptional signatures of small TF subsets with significantly increased expression in 202 neuroanatomical structures. These observations point to a regulatory paradigm that small sets of highly-expressed genes that are significantly enriched in distinct human brain regions are selected from genes encoding TFs bound to human-specific BDRRs, thus linking \"neuroanatomical transcriptional signatures\" of brain structures to TFs governing brain development. Together, our findings highlight TE-derived TFBS as central architects of primate brain evolution, providing both mechanistic insight and avenues for future discovery.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"80-126"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540900","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}
Chengyao Yang, Chaoyang Luo, Qiuping Wang, Xionghui Xu, Juan Zhang, Chengfa Zhao, Yuan Mu, Datian Lang, Wenxian Hu
{"title":"Insight into the Evolution of Mitochondrial Genetic Basis of Amphibious Adaptation in the Goby (Teleostei: Gobiidae).","authors":"Chengyao Yang, Chaoyang Luo, Qiuping Wang, Xionghui Xu, Juan Zhang, Chengfa Zhao, Yuan Mu, Datian Lang, Wenxian Hu","doi":"10.1007/s00239-025-10292-2","DOIUrl":"10.1007/s00239-025-10292-2","url":null,"abstract":"<p><p>The adaptation to terrestrial environments from aquatic environments has always been regarded as a major evolutionary transition in fishes, during which it has been accompanied with diverse phenotypic innovations. Mitochondrial energy metabolism fundamentally enables this shift, but the evolutionary trajectory and molecular mechanisms of mitogenomic adaptations to energy demands are poorly characterized. Mudskippers, a group of gobies with amphibious adaptive traits, serve as ideal models for studying energy metabolism during the water-to-land transition. To test whether amphibious adaptation in gobies corresponds to adaptive evolution in mitochondrial OXPHOS genes, we performed an in silico analysis of the 13 OXPHOS genes from the mitochondrial genomes of 33 goby species and two outgroups. The results showed that: (1) No matter ML or BI methods, four subfamilies Amblyopinae, Gobiinae, Gobionellinae, Oxudercinae are paraphyletic origin, except for subfamily Sicydiinae; besides, genus Scartelaos was first confirmed that it is paraphyletic origin. (2) 13 OXPHOS genes have been under the strong selective constraints, yet, the episodic positive selection was also detected, and ND4 and ATP8 evolution has been found to be under the accelerated evolution. Interestingly, (3) Significant divergent selection was detected between amphibious and fully aquatic lineages in 11 of the 13 OXPHOS genes (84%). And (4) the much stronger selective constraints were uncovered in amphibious lineages. To sum up, OXPHOS genes have undergone adaptive evolution with notable divergent patterns associated with the water-to-land transition during transition from water to land. These results provided some new insights into the genetic basis of amphibious adaptation in goby.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"3-13"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687444","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}
Chai-Ling Ho, Xuan-Zi Low, Wei-Kang Lee, John H Bothwell
{"title":"Genome-Wide Comparative and Phylogenetic Analysis of Putative Algal Carbohydrate Sulfotransferases.","authors":"Chai-Ling Ho, Xuan-Zi Low, Wei-Kang Lee, John H Bothwell","doi":"10.1007/s00239-025-10299-9","DOIUrl":"10.1007/s00239-025-10299-9","url":null,"abstract":"<p><p>Carbohydrate sulfotransferases (CHSTs) play a vital role in the production of sulfated polysaccharides (SPs) in algae by catalyzing the sulfation of carbohydrate moieties through the transfer of a sulfuryl group from the donor, 3'-phosphoadenosine 5'-phosphosulfate (PAPS). In the present study, putative algal CHSTs with a PF00685, PF03567. PF06990 and PF13469 domain were identified by HMMER search and Protein Basic Local Alignment Search Tool (BLAST) using the well-characterized human CHSTs as queries. Approximately half of the algal CHSTs that contained a PF00685 domain also possessed a PF13469 domain in an overlapping region. These CHSTs were structurally and phylogenetically distinct from algal CHSTs containing PF03567 or/and PF06990 domains. The PF00685/PF13469 domain is commonly found in Chlorophyta, while PF03567 and PF06990 domains are more prevalent in red algae and brown algae, respectively, reflecting the different types of SPs produced by these distinct phyla. Our phylogenetic analyses of algal CHSTs support the hypothesis of a polyphyletic origin, suggesting complex evolutionary histories involving both lineage-specific evolution and significant horizontal gene transfer (HGT) events between algae and organisms from other diverse taxa, including bacteria. In addition, the specificities of algal CHSTs for different carbohydrate moieties and site-specific sulfation patterns were inferred from the phylogenies of human CHSTs and the CHSTs from of algae with known SPs and chemical structures. This approach helps us to bridge the gap in knowledge, as a limited number of algal CHSTs have been biochemically characterized experimentally.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"231-249"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933705","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":"Molecular Phylogeny of \"Chemosensory Proteins\" in Bacteria and Arthropods: CSP as an Extremely Ancient Gene.","authors":"Jean-François Picimbon","doi":"10.1007/s00239-025-10297-x","DOIUrl":"10.1007/s00239-025-10297-x","url":null,"abstract":"<p><p>In this research paper, I provided a comprehensive overview of \"Chemosensory Proteins\" (CSPs), which have traditionally been thought to be involved in transporting odorant or tastant molecules to chemosensory receptors. However, CSPs are perplexingly expressed in various other organs and likely serve purposes other than chemosensing. By searching against microbial and crustacean protein databases, I found that CSPs are present not only in insects and other arthropods but also in bacteria. Given that CSPs are present from prokaryotes to insects and arthropods, and are expressed in many various tissues, I came to the conclusion that CSPs are unlikely to have purely chemosensory functions. This is consistent with most recent findings in the chemosensory field of Drosophila, where CSPs and odorant-binding proteins are thought to have functions beyond acting as odorant/tastant binding molecules.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"190-230"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119329","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":"Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.","authors":"Angelo Pavesi","doi":"10.1007/s00239-025-10284-2","DOIUrl":"10.1007/s00239-025-10284-2","url":null,"abstract":"<p><p>The discovery of translated alternative open reading frames (altORFs) in protein-coding regions has expanded the coding potential of viral, prokaryotic and eukaryotic genes. Experimental and computational approaches indicate that overlapping coding regions occur in mammals. In this study, I used a prediction method based on five criteria to detect novel altORFs in the human genes taken from the COSMIC Cancer Gene Census Database. Apart from the well characterized examples of human cancer-specific antigens expressed from altORF, the vast catalogue of nucleotide substitutions across cancer genes (the COSMIC database) is also likely to harbor previously uncharacterized altORFs. Under the five prediction criteria, I found 251 novel altORFs, 41 of which highly conserved in mammals and 60 uniquely resulting from nucleotide substitutions in the primary ORF of cancer genes. I found experimental evidence for 38% of the 251 novel altORFs from mass spectrometry and ribosome profiling databases. In particular, I found three altORFs in the proto-oncogene RET, three expressed altORfs in the isocitrate dehydrogenase-2 gene, and one expressed large altORF (498 nt) in the mutated TP53 gene. This study may offer clinical perspectives, because a potential source of cancer antigens may include antigens derived from translation of currently unannotated open reading frames. The altORFs detected in this study could be candidates for future experimental validation.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"62-79"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452093","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}
Zhen Zhao, Junye Ma, Qun Yang, Gert Wörheide, Dirk Erpenbeck
{"title":"First Report on Presence of Mitochondrial Introns in Freshwater Sponges, and Pseudogenic Evidence of Their Loss.","authors":"Zhen Zhao, Junye Ma, Qun Yang, Gert Wörheide, Dirk Erpenbeck","doi":"10.1007/s00239-025-10289-x","DOIUrl":"10.1007/s00239-025-10289-x","url":null,"abstract":"<p><p>Mitochondrial introns have a patchy distribution in sponge lineages. Here, we report on the finding of a group-II-intron in Eunapius rarus (Demospongiae, Spongillidae), which constitutes the first report of a mitochondrial intron in freshwater sponges. Group-II-introns are self-splicing ribozymes, and are particularly rare among sponge mitochondrial genomes. The intron contains complete open reading frames (ORFs), including typical intron-encoded proteins (IEPs). Phylogenetic analysis reveals that the intron is more closely related to those found in brown algae, and distant from other sponge group-II-introns, indicating an acquisition of this intron independent from other sponges. Remarkably, the congeneric E. fragilis does not possess this intron in their mitochondrial genome. However, we found pseudogenic copies of the E. rarus group-II-intron in the nuclear genome of E. fragilis, which indicates patterns of group-II-intron presence and their pseudogene transposition into the nuclear genomes in sponges for the first time. Our results show that a group-II-intron must have been present in the last common ancestor of both Eunapius mt genomes, and subsequently lost in E. fragilis, rather than independent acquisition. Consequently, our findings provide an explanation for the patchy distribution of introns in sponges as a result of frequent losses, besides multiple acquisitions.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"19-23"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12920757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ksenia Macias Calix, Antara Anika Piya, Raquel Assis
{"title":"Correlated Evolution Drives Structural Convergence of Interacting Proteins.","authors":"Ksenia Macias Calix, Antara Anika Piya, Raquel Assis","doi":"10.1007/s00239-025-10291-3","DOIUrl":"10.1007/s00239-025-10291-3","url":null,"abstract":"<p><p>Understanding the relationship between protein structures and their interactions is a fundamental biological problem. Here we broadly tackle this problem by examining associations between protein structural features and interaction patterns in rodents and yeast-two highly divergent taxa from different kingdoms. In both taxa, we uncover positive correlations between intrinsic disorders of interacting proteins, consistent with a prior study showing stronger affinity between proteins with similar structures. However, closer examination reveals that these relationships are restricted to proteins involved in evolutionarily conserved interactions, or interologs. We also find that interologs generally exhibit more similar protein structures and less evolutionary structural divergence than non-interologs, supporting the hypothesis that conserved interactions are associated with structural convergence of interacting proteins. Further analyses show that interologs are typically less intrinsically disordered and play more central functional roles than non-interologs, suggesting that these structural similarities may help preserve stable interactions involved in essential biological processes. Overall, this study underscores the interconnected evolution of protein structures and their interactions, illustrating how the optimization of protein fitness landscapes for both structural and functional stability may promote structural convergence across divergent taxa.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"136-148"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12920738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}