{"title":"High Nucleotide Skew Palindromic DNA Sequences Function as Potential Replication Origins due to their Unzipping Propensity.","authors":"Parthasarathi Sahu, Sashikanta Barik, Koushik Ghosh, Hemachander Subramanian","doi":"10.1007/s00239-024-10202-y","DOIUrl":"https://doi.org/10.1007/s00239-024-10202-y","url":null,"abstract":"<p><p>Locations of DNA replication initiation in prokaryotes, called \"origins of replication\", are well-characterized. However, a mechanistic understanding of the sequence dependence of the local unzipping of double-stranded DNA, the first step towards replication initiation, is lacking. Here, utilizing a Markov chain model that was created to address the directional nature of DNA unzipping and replication, we model the sequence dependence of local melting of double-stranded linear DNA segments. We show that generalized palindromic sequences with high nucleotide skews have a low kinetic barrier for local melting near melting temperatures. This allows for such sequences to function as potential replication origins. We support our claim with evidence for high-skew palindromic sequences within the replication origins of mitochondrial DNA, bacteria, archaea and plasmids.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307910","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":"Structural and Evolutionary Analysis of Proteins Endowed with a Nucleotidyltransferase, or Non-canonical Palm, Catalytic Domain","authors":"Rodrigo Jácome","doi":"10.1007/s00239-024-10207-7","DOIUrl":"https://doi.org/10.1007/s00239-024-10207-7","url":null,"abstract":"<p>Many polymerases and other proteins are endowed with a catalytic domain belonging to the nucleotidyltransferase fold, which has also been deemed the non-canonical palm domain, in which three conserved acidic residues coordinate two divalent metal ions. Tertiary structure-based evolutionary analyses provide valuable information when the phylogenetic signal contained in the primary structure is blurry or has been lost, as is the case with these proteins. Pairwise structural comparisons of proteins with a nucleotidyltransferase fold were performed in the PDBefold web server: the RMSD, the number of superimposed residues, and the Qscore were obtained. The structural alignment score (RMSD × 100/number of superimposed residues) and the 1-Qscore were calculated, and distance matrices were constructed, from which a dendogram and a phylogenetic network were drawn for each score. The dendograms and the phylogenetic networks display well-defined clades, reflecting high levels of structural conservation within each clade, not mirrored by primary sequence. The conserved structural core between all these proteins consists of the catalytic nucleotidyltransferase fold, which is surrounded by different functional domains. Hence, many of the clades include proteins that bind different substrates or partake in non-related functions. Enzymes endowed with a nucleotidyltransferase fold are present in all domains of life, and participate in essential cellular and viral functions, which suggests that this domain is very ancient. Despite the loss of evolutionary traces in their primary structure, tertiary structure-based analyses allow us to delve into the evolution and functional diversification of the NT fold.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":"32 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267091","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}
Guillermina Hill-Terán, Julieta Petrich, Maria Lorena Falcone Ferreyra, Manuel J. Aybar, Gabriela Coux
{"title":"Untangling Zebrafish Genetic Annotation: Addressing Complexities and Nomenclature Issues in Orthologous Evaluation of TCOF1 and NOLC1","authors":"Guillermina Hill-Terán, Julieta Petrich, Maria Lorena Falcone Ferreyra, Manuel J. Aybar, Gabriela Coux","doi":"10.1007/s00239-024-10200-0","DOIUrl":"https://doi.org/10.1007/s00239-024-10200-0","url":null,"abstract":"<p>Treacher Collins syndrome (TCS) is a genetic disorder affecting facial development, primarily caused by mutations in the <i>TCOF1</i> gene. TCOF1, along with NOLC1, play important roles in ribosomal RNA transcription and processing. Previously, a zebrafish model of TCS successfully recapitulated the main characteristics of the syndrome by knocking down the expression of a gene on chromosome 13 (coding for Uniprot ID B8JIY2), which was identified as the <i>TCOF1</i> orthologue. However, database updates renamed this gene as <i>nolc1</i> and the zebrafish database (ZFIN) identified a different gene on chromosome 14 as the <i>TCOF1</i> orthologue (coding for Uniprot ID E7F9D9). NOLC1 and TCOF1 are large proteins with unstructured regions and repetitive sequences that complicate alignments and comparisons. Also, the additional whole genome duplication of teleosts sets further difficulty. In this study, we present evidence that endorses that <i>NOLC1</i> and <i>TCOF1</i> are paralogs, and that the zebrafish gene on chromosome 14 is a low-complexity LisH domain-containing factor that displays homology to NOLC1 but lacks essential sequence features to accomplish TCOF1 nucleolar functions. Our analysis also supports the idea that zebrafish, as has been suggested for other non-tetrapod vertebrates, lack the <i>TCOF1</i> gene that is associated with tripartite nucleolus. Using BLAST searches in a group of teleost genomes, we identified fish-specific sequences similar to E7F9D9 zebrafish protein. We propose naming them “LisH-containing Low Complexity Proteins” (LLCP). Interestingly, the gene on chromosome 13 <i>(nolc1</i>) displays the sequence features, developmental expression patterns, and phenotypic impact of depletion that are characteristic of <i>TCOF1</i> functions. These findings suggest that in teleost fish, the nucleolar functions described for both <i>NOLC1</i> and <i>TCOF1</i> mediated by their repeated motifs, are carried out by a single gene, <i>nolc1</i>. Our study, which is mainly based on computational tools available as free web-based algorithms, could help to solve similar conflicts regarding gene orthology in zebrafish.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":"5 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194309","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":"Recurrent Independent Pseudogenization Events of the Sperm Fertilization Gene ZP3r in Apes and Monkeys","authors":"J. A. Carlisle, D. H. Gurbuz, W. J. Swanson","doi":"10.1007/s00239-024-10192-x","DOIUrl":"https://doi.org/10.1007/s00239-024-10192-x","url":null,"abstract":"<p>Many reproductive proteins show signatures of rapid evolution through sequence divergence and duplication. These features of reproductive genes may complicate the detection of orthologs across taxa, making it difficult to connect studies in model systems to human biology. In mice, ZP3r/sp56 is a binding partner to the egg coat protein ZP3 and may mediate induction of the acrosome reaction, a crucial step in fertilization. In rodents, ZP3r, as a member of the Regulators of Complement Activation cluster, is surrounded by paralogs, some of which have been shown to be evolving under positive selection. Although primate egg coats also contain ZP3, sequence divergence paired with paralogous relationships with neighboring genes has complicated the accurate identification of the human ZP3r ortholog. Here, we phylogenetically and syntenically resolve that the human ortholog of ZP3r is the pseudogene <i>C4BPAP1</i>. We investigate the evolution of this gene within primates. We observe independent pseudogenization events of ZP3r in all Apes with the exception of Orangutans, and independent pseudogenization events in many monkey species. ZP3r in both primates that retain ZP3r and in rodents contains positively selected sites. We hypothesize that redundant mechanisms mediate ZP3 recognition in mammals and ZP3r’s relative importance to ZP recognition varies across species.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194311","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}
Shinde Nikhil, Habeeb Shaikh Mohideen, Raja Natesan Sella
{"title":"Unveiling the Genomic Symphony: Identification Cultivar-Specific Genes and Enhanced Insights on Sweet Sorghum Genomes Through Comprehensive superTranscriptomic Analysis","authors":"Shinde Nikhil, Habeeb Shaikh Mohideen, Raja Natesan Sella","doi":"10.1007/s00239-024-10198-5","DOIUrl":"https://doi.org/10.1007/s00239-024-10198-5","url":null,"abstract":"<p>Sorghum (<i>Sorghum bicolor (L.) Moench</i>) is a multipurpose crop grown for food, fodder, and bioenergy production. Its cultivated varieties, along with their wild counterparts, contribute to the core genetic pool. Despite the availability of several re-sequenced sorghum genomes, a variable portion of sorghum genomes is not reported during reference genome assembly and annotation. The present analysis used 223 publicly available RNA-seq datasets from seven sweet sorghum cultivars to construct superTranscriptome. This approach yielded 45,864 Representative Transcript Assemblies (RTAs) that showcased intriguing Presence/Absence Variation (PAV) across 15 published sorghum genomes. We found 301 superTranscripts were exclusive to sweet sorghum, including 58 de novo genes encoded core and linker histones, zinc finger domains, glucosyl transferases, cellulose synthase, etc. The superTranscriptome added 2,802 new protein-coding genes to the Sweet Sorghum Reference Genome (SSRG), of which 559 code for different transcription factors (TFs). Our analysis revealed that MULE-like transposases were abundant in the sweet sorghum genome and could play a hidden role in the evolution of sweet sorghum. We observed large deletions in the D locus and terminal deletions in four other NAC encoding loci in the SSRG compared to its wild progenitor (353) suggesting non-functional NAC genes contributed to trait development in sweet sorghum. Moreover, superTranscript-based methods for Differential Exon Usage (DEU) and Differential Gene Expression (DGE) analyses were more accurate than those based on the SSRG. This study demonstrates that the superTranscriptome can enhance our understanding of fundamental sorghum mechanisms, improve genome annotations, and potentially even replace the reference genome.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":"12 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194310","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":"On the Nature of the Last Common Ancestor: A Story from its Translation Machinery","authors":"Mario Rivas, George E. Fox","doi":"10.1007/s00239-024-10199-4","DOIUrl":"https://doi.org/10.1007/s00239-024-10199-4","url":null,"abstract":"<p>The Last Common Ancestor (LCA) is understood as a hypothetical population of organisms from which all extant living creatures are thought to have descended. Its biology and environment have been and continue to be the subject of discussions within the scientific community. Since the first bacterial genomes were obtained, multiple attempts to reconstruct the genetic content of the LCA have been made. In this review, we compare 10 of the most extensive reconstructions of the gene content possessed by the LCA as they relate to aspects of the translation machinery. Although each reconstruction has its own methodological biases and many disagree in the metabolic nature of the LCA all, to some extent, indicate that several components of the translation machinery are among the most conserved genetic elements. The datasets from each reconstruction clearly show that the LCA already had a largely complete translational system with a genetic code already in place and therefore was not a <i>progenote</i>. Among these features several ribosomal proteins, transcription factors like IF2, EF-G, and EF-Tu and both class I and class II aminoacyl tRNA synthetases were found in essentially all reconstructions. Due to the limitations of the various methodologies, some features such as the occurrence of rRNA posttranscriptional modified bases are not fully addressed. However, conserved as it is, non-universal ribosomal features found in various reconstructions indicate that LCA’s translation machinery was still evolving, thereby acquiring the domain specific features in the process. Although progenotes from the pre-LCA likely no longer exist recent results obtained by unraveling the early history of the ribosome and other genetic processes can provide insight to the nature of the pre-LCA world.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":"55 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194312","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 Cancer-Resisting Evolutionary Adaptations in Wild Animals and Applications for Human Oncology","authors":"Bokai K. Zhang, Leonard Gines","doi":"10.1007/s00239-024-10204-w","DOIUrl":"https://doi.org/10.1007/s00239-024-10204-w","url":null,"abstract":"<p>This literature review is to present a new direction in developing better treatment or preventive measures. The larger the body of an organism, the more numerous the cells, which theoretically lead to a higher risk of cancer. However, observational studies suggest the lack of correlation between body size and cancer risk, which is known as Peto’s paradox. The corollary of Peto’s paradox is that large organisms must be cancer-resistant. Further investigation of the anti-cancer mechanisms in each species could be potentially rewarding, and how the anti-cancer mechanisms found in wild animals can help influence and develop more effective cancer treatment in humans is the main focus of this literature review. Due to a lack of research and understanding of the exact molecular mechanisms of the researched species, only a few (Elephants and rodents) that have been extensively researched have made substantive contributions to human oncology. A new research direction is to investigate the positively selective genes that are related to cancer resistance and see if homologous genes are presented in humans. Despite the great obstacle of applying anti-cancer mechanisms to the human body from phylogenetically distant species, this research direction of gaining insights through investigating cancer-resisting evolutionary adaptations in wild animals has great potential in human oncology research.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":"4 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194313","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":"Intrinsic Disorder and Other Malleable Arsenals of Evolved Protein Multifunctionality.","authors":"Asifa Aftab, Souradeep Sil, Seema Nath, Anirneya Basu, Sankar Basu","doi":"10.1007/s00239-024-10196-7","DOIUrl":"https://doi.org/10.1007/s00239-024-10196-7","url":null,"abstract":"<p><p>Microscopic evolution at the functional biomolecular level is an ongoing process. Leveraging functional and high-throughput assays, along with computational data mining, has led to a remarkable expansion of our understanding of multifunctional protein (and gene) families over the past few decades. Various molecular and intermolecular mechanisms are now known that collectively meet the cumulative multifunctional demands in higher organisms along an evolutionary path. This multitasking ability is attributed to a certain degree of intrinsic or adapted flexibility at the structure-function level. Evolutionary diversification of structure-function relationships in proteins highlights the functional importance of intrinsically disordered proteins/regions (IDPs/IDRs) which are highly dynamic biological soft matter. Multifunctionality is favorably supported by the fluid-like shapes of IDPs/IDRs, enabling them to undergo disorder-to-order transitions upon binding to different molecular partners. Other new malleable members of the protein superfamily, such as those involved in fold-switching, also undergo structural transitions. This new insight diverges from all traditional notions of functional singularity in enzyme classes and emphasizes a far more complex, multi-layered diversification of protein functionality. However, a thorough review in this line, focusing on flexibility and function-driven structural transitions related to evolved multifunctionality in proteins, is currently missing. This review attempts to address this gap while broadening the scope of multifunctionality beyond single protein sequences. It argues that protein intrinsic disorder is likely the most striking mechanism for expressing multifunctionality in proteins. A phenomenological analogy has also been drawn to illustrate the increasingly complex nature of modern digital life, driven by the need for multitasking, particularly involving media.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108231","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":"Principles of Molecular Evolution: Concepts from Non-equilibrium Thermodynamics for the Multilevel Theory of Learning.","authors":"Jens Smiatek","doi":"10.1007/s00239-024-10195-8","DOIUrl":"https://doi.org/10.1007/s00239-024-10195-8","url":null,"abstract":"<p><p>We present a non-equilibrium thermodynamics approach to the multilevel theory of learning for the study of molecular evolution. This approach allows us to study the explicit time dependence of molecular evolutionary processes and their impact on entropy production. Interpreting the mathematical expressions, we can show that two main contributions affect entropy production of molecular evolution processes which can be identified as mutation and gene transfer effects. Accordingly, our results show that the optimal adaptation of organisms to external conditions in the context of evolutionary processes is driven by principles of minimum entropy production. Such results can also be interpreted as the basis of some previous postulates of the theory of learning. Although our macroscopic approach requires certain simplifications, it allows us to interpret molecular evolutionary processes using thermodynamic descriptions with reference to well-known biological processes.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108232","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}