Journal of Molecular Evolution最新文献

{"title":"A Law of Redundancy Compounds the Problem of Cancer and Precision Medicine.","authors":"Rama S Singh","doi":"10.1007/s00239-023-10131-2","DOIUrl":"10.1007/s00239-023-10131-2","url":null,"abstract":"<p><p>Genetics and molecular biology research have progressed for over a century; however, no laws of biology resembling those of physics have been identified, despite the expectations of some physicists. It may be that it is not the properties of matter alone but evolved properties of matter in combination with atomic physics and chemistry that gave rise to the origin and complexity of life. It is proposed that any law of biology must also be a product of evolution that co-evolved with the origin and progression of life. It was suggested that molecular complexity and redundancy exponentially increase over time and have the following relationship: DNA sequence complexity (Cd) < molecular complexity (Cm) < phenotypic complexity (Cp). This study presents a law of redundancy, which together with the law of complexity, is proposed as an evolutionary law of biology. Molecular complexity and redundancy are inseparable aspects of biochemical pathways, and molecular redundancy provides the first line of defense against environmental challenges, including those of deleterious mutations. Redundancy can create problems for precision medicine because in addition to the issues arising from the involvement of multiple genes, redundancy arising from alternate pathways between genotypes and phenotypes can complicate gene detection for complex diseases and mental disorders. This study uses cancer as an example to show how cellular complexity, molecular redundancy, and hidden variation affect the ability of cancer cells to evolve and evade detection and elimination. Characterization of alternate biochemical pathways or \"escape routes\" can provide a step in the fight against cancer.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10597872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10519926","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}

{"title":"Domain Architecture Based Methods for Comparative Functional Genomics Toward Therapeutic Drug Target Discovery.","authors":"Pavan Gollapalli,&nbsp;Sushmitha Rudrappa,&nbsp;Vadlapudi Kumar,&nbsp;Hulikal Shivashankara Santosh Kumar","doi":"10.1007/s00239-023-10129-w","DOIUrl":"10.1007/s00239-023-10129-w","url":null,"abstract":"<p><p>Genes duplicate, mutate, recombine, fuse or fission to produce new genes, or when genes are formed from de novo, novel functions arise during evolution. Researchers have tried to quantify the causes of these molecular diversification processes to know how these genes increase molecular complexity over a period of time, for instance protein domain organization. In contrast to global sequence similarity, protein domain architectures can capture key structural and functional characteristics, making them better proxies for describing functional equivalence. In Prokaryotes and eukaryotes it has proven that, domain designs are retained over significant evolutionary distances. Protein domain architectures are now being utilized to categorize and distinguish evolutionarily related proteins and find homologs among species that are evolutionarily distant from one another. Additionally, structural information stored in domain structures has accelerated homology identification and sequence search methods. Tools for functional protein annotation have been developed to discover, protein domain content, domain order, domain recurrence, and domain position as all these contribute to the prediction of protein functional accuracy. In this review, an attempt is made to summarise facts and speculations regarding the use of protein domain architecture and modularity to identify possible therapeutic targets among cellular activities based on the understanding their linked biological processes.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10074646","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":"Kinetic Modeling and Parameter Estimation of a Prebiotic Peptide Reaction Network.","authors":"Hayley Boigenzahn, Leonardo D González, Jaron C Thompson, Victor M Zavala, John Yin","doi":"10.1007/s00239-023-10132-1","DOIUrl":"10.1007/s00239-023-10132-1","url":null,"abstract":"<p><p>Although our understanding of how life emerged on Earth from simple organic precursors is speculative, early precursors likely included amino acids. The polymerization of amino acids into peptides and interactions between peptides are of interest because peptides and proteins participate in complex interaction networks in extant biology. However, peptide reaction networks can be challenging to study because of the potential for multiple species and systems-level interactions between species. We developed and employed a computational network model to describe reactions between amino acids to form di-, tri-, and tetra-peptides. Our experiments were initiated with two of the simplest amino acids, glycine and alanine, mediated by trimetaphosphate-activation and drying to promote peptide bond formation. The parameter estimates for bond formation and hydrolysis reactions in the system were found to be poorly constrained due to a network property known as sloppiness. In a sloppy model, the behavior mostly depends on only a subset of parameter combinations, but there is no straightforward way to determine which parameters should be included or excluded. Despite our inability to determine the exact values of specific kinetic parameters, we could make reasonably accurate predictions of model behavior. In short, our modeling has highlighted challenges and opportunities toward understanding the behaviors of complex prebiotic chemical experiments.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41136124","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":"Phenotype Design Space Provides a Mechanistic Framework Relating Molecular Parameters to Phenotype Diversity Available for Selection.","authors":"Michael A Savageau","doi":"10.1007/s00239-023-10127-y","DOIUrl":"10.1007/s00239-023-10127-y","url":null,"abstract":"<p><p>Two long-standing challenges in theoretical population genetics and evolution are predicting the distribution of phenotype diversity generated by mutation and available for selection, and determining the interaction of mutation, selection and drift to characterize evolutionary equilibria and dynamics. More fundamental for enabling such predictions is the current inability to causally link genotype to phenotype. There are three major mechanistic mappings required for such a linking - genetic sequence to kinetic parameters of the molecular processes, kinetic parameters to biochemical system phenotypes, and biochemical phenotypes to organismal phenotypes. This article introduces a theoretical framework, the Phenotype Design Space (PDS) framework, for addressing these challenges by focusing on the mapping of kinetic parameters to biochemical system phenotypes. It provides a quantitative theory whose key features include (1) a mathematically rigorous definition of phenotype based on biochemical kinetics, (2) enumeration of the full phenotypic repertoire, and (3) functional characterization of each phenotype independent of its context-dependent selection or fitness contributions. This framework is built on Design Space methods that relate system phenotypes to genetically determined parameters and environmentally determined variables. It also has the potential to automate prediction of phenotype-specific mutation rate constants and equilibrium distributions of phenotype diversity in microbial populations undergoing steady-state exponential growth, which provides an ideal reference to which more realistic cases can be compared. Although the framework is quite general and flexible, the details will undoubtedly differ for different functions, organisms and contexts. Here a hypothetical case study involving a small molecular system, a primordial circadian clock, is used to introduce this framework and to illustrate its use in a particular case. The framework is built on fundamental biochemical kinetics. Thus, the foundation is based on linear algebra and reasonable physical assumptions, which provide numerous opportunities for experimental testing and further elaboration to deal with complex multicellular organisms that are currently beyond its scope. The discussion provides a comparison of results from the PDS framework with those from other approaches in theoretical population genetics.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067214","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}

{"title":"A Micro-evolutionary Change in Target Binding Sites as a Key Determinant of Ultrabithorax Function in Drosophila.","authors":"Soumen Khan,&nbsp;Saurabh J Pradhan,&nbsp;Guillaume Giraud,&nbsp;Françoise Bleicher,&nbsp;Rachel Paul,&nbsp;Samir Merabet,&nbsp;L S Shashidhara","doi":"10.1007/s00239-023-10123-2","DOIUrl":"10.1007/s00239-023-10123-2","url":null,"abstract":"<p><p>Hox genes encode Homeodomain-containing transcription factors, which specify segmental identities along the anterior-posterior axis. Functional changes in Hox genes have been directly implicated in the evolution of body plans across the metazoan lineage. The Hox protein Ultrabithorax (Ubx) is expressed and required in developing third thoracic (T3) segments in holometabolous insects studied so far, particularly, of the order Coleoptera, Lepidoptera and Diptera. Ubx function is key to specify differential development of the second (T2) and T3 thoracic segments in these insects. While Ubx is expressed in the third thoracic segment in developing larvae of Hymenopteran Apis mellifera, the morphological differences between T2 and T3 are subtle. To identify evolutionary changes that are behind the differential function of Ubx in Drosophila and Apis, which are diverged for more than 350 million years, we performed comparative analyses of genome wide Ubx-binding sites between these two insects. Our studies reveal that a motif with a TAAAT core is a preferred binding site for Ubx in Drosophila, but not in Apis. Biochemical and transgenic assays suggest that in Drosophila, the TAAAT core sequence in the Ubx binding sites is required for Ubx-mediated regulation of two of its target genes studied here; CG13222, a gene that is normally upregulated by Ubx and vestigial (vg), whose expression is repressed by Ubx in T3. Interestingly, changing the TAAT site to a TAAAT site was sufficient to bring an otherwise unresponsive enhancer of the vg gene from Apis under the control of Ubx in a Drosophila transgenic assay. Taken together, our results suggest an evolutionary mechanism by which critical wing patterning genes might have come under the regulation of Ubx in the Dipteran lineage.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9667747","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 Evolution of Aryl Hydrocarbon Receptor Signaling Pathway Genes.","authors":"Diksha Bhalla,&nbsp;Vera van Noort","doi":"10.1007/s00239-023-10124-1","DOIUrl":"10.1007/s00239-023-10124-1","url":null,"abstract":"<p><p>The Aryl hydrocarbon receptor is an ancient transcriptional factor originally discovered as a sensor of dioxin. In addition to its function as a receptor of environmental toxicants, it plays an important role in development. Although a significant amount of research has been carried out to understand the AHR signal transduction pathway and its involvement in species' susceptibility to environmental toxicants, none of them to date has comprehensively studied its evolutionary origins. Studying the evolutionary origins of molecules can inform ancestral relationships of genes. The vertebrate genome has been shaped by two rounds of whole-genome duplications (WGD) at the base of vertebrate evolution approximately 600 million years ago, followed by lineage-specific gene losses, which often complicate the assignment of orthology. It is crucial to understand the evolutionary origins of this transcription factor and its partners, to distinguish orthologs from ancient non-orthologous homologs. In this study, we have investigated the evolutionary origins of proteins involved in the AHR pathway. Our results provide evidence of gene loss and duplications, crucial for understanding the functional connectivity of humans and model species. Multiple studies have shown that 2R-ohnologs (genes and proteins that have survived from the 2R-WGD) are enriched in signaling components relevant to developmental disorders and cancer. Our findings provide a link between the AHR pathway's evolutionary trajectory and its potential mechanistic involvement in pathogenesis.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10088426","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":"Informatic Capabilities of Translation and Its Implications for the Origins of Life.","authors":"Bruno Cuevas-Zuviría,&nbsp;Zachary R Adam,&nbsp;Aaron D Goldman,&nbsp;Betül Kaçar","doi":"10.1007/s00239-023-10125-0","DOIUrl":"10.1007/s00239-023-10125-0","url":null,"abstract":"<p><p>The ability to encode and convert heritable information into molecular function is a defining feature of life as we know it. The conversion of information into molecular function is performed by the translation process, in which triplets of nucleotides in a nucleic acid polymer (mRNA) encode specific amino acids in a protein polymer that folds into a three-dimensional structure. The folded protein then performs one or more molecular activities, often as one part of a complex and coordinated physiological network. Prebiotic systems, lacking the ability to explicitly translate information between genotype and phenotype, would have depended upon either chemosynthetic pathways to generate its components-constraining its complexity and evolvability- or on the ambivalence of RNA as both carrier of information and of catalytic functions-a possibility which is still supported by a very limited set of catalytic RNAs. Thus, the emergence of translation during early evolutionary history may have allowed life to unmoor from the setting of its origin. The origin of translation machinery also represents an entirely novel and distinct threshold of behavior for which there is no abiotic counterpart-it could be the only known example of computing that emerged naturally at the chemical level. Here we describe translation machinery's decoding system as the basis of cellular translation's information-processing capabilities, and the four operation types that find parallels in computer systems engineering that this biological machinery exhibits.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908831","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 Analysis of Diverse Polynucleotide Kinase Clp1 Family Proteins in Eukaryotes: Three Unique Clp1 Proteins of Trypanosoma brucei.","authors":"Motofumi Saito,&nbsp;Rerina Inose,&nbsp;Asako Sato,&nbsp;Masaru Tomita,&nbsp;Haruo Suzuki,&nbsp;Akio Kanai","doi":"10.1007/s00239-023-10128-x","DOIUrl":"10.1007/s00239-023-10128-x","url":null,"abstract":"<p><p>The Clp1 family proteins, consisting of the Clp1 and Nol9/Grc3 groups, have polynucleotide kinase (PNK) activity at the 5' end of RNA strands and are important enzymes in the processing of some precursor RNAs. However, it remains unclear how this enzyme family diversified in the eukaryotes. We performed a large-scale molecular evolutionary analysis of the full-length genomes of 358 eukaryotic species to classify the diverse Clp1 family proteins. The average number of Clp1 family proteins in eukaryotes was 2.3 ± 1.0, and most representative species had both Clp1 and Nol9/Grc3 proteins, suggesting that the Clp1 and Nol9/Grc3 groups were already formed in the eukaryotic ancestor by gene duplication. We also detected an average of 4.1 ± 0.4 Clp1 family proteins in members of the protist phylum Euglenozoa. For example, in Trypanosoma brucei, there are three genes of the Clp1 group and one gene of the Nol9/Grc3 group. In the Clp1 group proteins encoded by these three genes, the C-terminal domains have been replaced by unique characteristics domains, so we designated these proteins Tb-Clp1-t1, Tb-Clp1-t2, and Tb-Clp1-t3. Experimental validation showed that only Tb-Clp1-t2 has PNK activity against RNA strands. As in this example, N-terminal and C-terminal domain replacement also contributed to the diversification of the Clp1 family proteins in other eukaryotic species. Our analysis also revealed that the Clp1 family proteins in humans and plants diversified through isoforms created by alternative splicing.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037755","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}

{"title":"Pseudogenization of the Hair-Related Genes PADI3 and S100A3 in Cetaceans and Hippopotamus amphibius.","authors":"Kyomi Nagasawa, Takashi Kitano","doi":"10.1007/s00239-023-10133-0","DOIUrl":"10.1007/s00239-023-10133-0","url":null,"abstract":"<p><p>Hair-related genes in mammals play important roles in the development and maintenance of hair and other keratinous structures in mammals. The peptidyl arginine deiminase 3 (PADI3) gene encodes an enzyme that catalyzes the conversion of arginine residues to citrulline. The S100 calcium binding protein A3 (S100A3) gene encodes a protein that is highly expressed in the hair cuticle and contains arginine residues that are converted to citrullines by PADI enzymes. In this study, we investigated the pseudogenization events of PADI3 and S100A3 in cetaceans and Hippopotamus amphibius. We found that PADI3 underwent three independent pseudogenization events during cetacean evolution, in baleen whales, toothed cetaceans other than Physeter catodon, and P. catodon. Notably, the entire PADI3 gene is absent in the baleen whales. Pseudogenization of S100A3 occurred independently in cetaceans and H. amphibius. Interestingly, we found that in cetaceans S100A3 underwent pseudogenization before PADI3, suggesting that differential selection pressures were acting on the two genes. Our findings provide valuable insights into the molecular evolution of these genes in cetaceans and hippopotamuses, highlighting their importance for understanding the evolution of hair-related genes.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135796","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":"Left-Right Reversal Recurrently Evolved Regardless of Diaphanous-Related Formin Gene Duplication or Loss in Snails.","authors":"Takeshi Noda,&nbsp;Noriyuki Satoh,&nbsp;Edmund Gittenberger,&nbsp;Takahiro Asami","doi":"10.1007/s00239-023-10130-3","DOIUrl":"10.1007/s00239-023-10130-3","url":null,"abstract":"<p><p>Bilateria exhibit whole-body handedness in internal structure. This left-right polarity is evolutionarily conserved with virtually no reversed extant lineage, except in molluscan Gastropoda. Phylogenetically independent snail groups contain both clockwise-coiled (dextral) and counterclockwise-coiled (sinistral) taxa that are reversed from each other in bilateral handedness as well as in coiling direction. Within freshwater Hygrophila, Lymnaea with derived dextrality have diaphanous related formin (diaph) gene duplicates, while basal sinistral groups possess one diaph gene. In terrestrial Stylommatophora, dextral Bradybaena also have diaph duplicates. Defective maternal expression of one of those duplicates gives rise to sinistral hatchlings in Lymnaea and handedness-mixed broods in Bradybaena, through polarity change in spiral cleavage of embryos. These findings led to the hypothesis that diaph duplication was crucial for the evolution of dextrality by reversal. The present study discovered that diaph duplication independently occurred four times and its duplicate became lost twice in gastropods. The dextrality of Bradybaena represents the ancestral handedness conserved across gastropods, unlike the derived dextrality of Lymnaea. Sinistral lineages recurrently evolved by reversal regardless of whether diaph had been duplicated. Amongst the seven formin gene subfamilies, diaph has most thoroughly been conserved across eukaryotes of the 14 metazoan phyla and choanoflagellate. Severe embryonic mortalities resulting from insufficient expression of the duplicate in both of Bradybaena and Lymnaea also support that diaph duplicates bare general roles for cytoskeletal dynamics other than controlling spiralian handedness. Our study rules out the possibility that diaph duplication or loss played a primary role for reversal evolution.</p>","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135795","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}