Molecular Diversification Research Articles

Comprehensive molecular phylogeny and diversification of snappers (Actinopterygii: Perciformes: Lutjanidae) from the Odisha coast, Bay of Bengal, India: taxonomy and distribution

Comprehensive molecular phylogeny and diversification of snappers (Actinopterygii: Perciformes: Lutjanidae) from the Odisha coast, Bay of Bengal, India: taxonomy and distribution

C(sp3)-H (N-Phenyltetrazole)thiolation as an Enabling Tool for Molecular Diversification.

Methods enabling the broad diversification of C(sp3)-H bonds from a common intermediate are especially valuable in chemical synthesis. Herein, we report a site-selective (N-phenyltetrazole)thiolation of aliphatic and (hetero)benzylic C(sp3)-H bonds using a commercially available disulfide to access N-phenyltetrazole thioethers. The thioether products are readily elaborated in diverse fragment couplings for C-C, C-O, or C-N construction. The C-H functionalization proceeds via a radical-chain pathway involving hydrogen atom transfer by the electron-poor N-phenyltetrazolethiyl radical. Hexafluoroisopropanol was found to be essential to reactions involving aliphatic C(sp3)-H thiolation, with computational analysis consistent with dual hydrogen bonding of the N-phenyltetrazolethiyl radical imparting increased radical electrophilicity to facilitate the hydrogen atom transfer. Substrate is limiting reagent in all cases, and the reaction displays an exceptional functional group tolerance well suited to applications in late-stage diversification.

C(sp3)−H (N‐Phenyltetrazole)thiolation as an Enabling Tool for Molecular Diversification

AbstractMethods enabling the broad diversification of C(sp3)−H bonds from a common intermediate are especially valuable in chemical synthesis. Herein, we report a site‐selective (N‐phenyltetrazole)thiolation of aliphatic and (hetero)benzylic C(sp3)−H bonds using a commercially available disulfide to access N‐phenyltetrazole thioethers. The thioether products are readily elaborated in diverse fragment couplings for C−C, C−O, or C−N construction. The C−H functionalization proceeds via a radical‐chain pathway involving hydrogen atom transfer by the electron‐poor N‐phenyltetrazolethiyl radical. Hexafluoroisopropanol was found to be essential to reactions involving aliphatic C(sp3)−H thiolation, with computational analysis consistent with dual hydrogen bonding of the N‐phenyltetrazolethiyl radical imparting increased radical electrophilicity to facilitate the hydrogen atom transfer. Substrate is limiting reagent in all cases, and the reaction displays an exceptional functional group tolerance well suited to applications in late‐stage diversification.

Molecular evolution and functional diversification of metal tolerance protein families in cereals plants and function of maize MTP protein

Plants employ metal tolerance proteins (MTPs) to confer tolerance by sequestering excess ions into vacuoles. MTPs belong to the cation diffusion facilitator (CDF) family, which facilitates the transport of divalent transition metal cations. In this study, we conducted a comprehensive analysis of the MTP gene families across 21 plant species, including maize (Zea mays). A total of 247 MTP genes were identified within these plant genomes and categorized into distinct subgroups, namely Zn-CDF, Mn-CDF, and Fe/Zn-CDF, based on phylogenetic analyses. This investigation encompassed the characterization of genomic distribution, gene structures, cis-regulatory elements, collinearity relationships, and gene ontology functions associated with MTPs. Transcriptomic analyses unveiled stress-specific expression patterns of MTP genes under various abiotic stresses. Moreover, quantitative RT-PCR assays were employed to assess maize MTP gene responses to diverse heavy metal stress conditions. Functional validation of metal tolerance roles was achieved through heterologous expression in yeast. This integrated evolutionary scrutiny of MTP families in cereals furnishes a valuable framework for the elucidation of MTP functions in subsequent studies. Notably, the prioritized MTP gene ZmMTP6 emerged as a positive regulator of plant Cd tolerance, thereby offering a pivotal genetic asset for the development of Cd-tolerant crops, particularly maize cultivars.

New insights into the molecular phylogeny, biogeographical history, and diversification of Amblyomma ticks (Acari: Ixodidae) based on mitogenomes and nuclear sequences.

Amblyomma is the third most diversified genus of Ixodidae that is distributed across the Indomalayan, Afrotropical, Australasian (IAA), Nearctic and Neotropical biogeographic ecoregions, reaching in the Neotropic its highest diversity. There have been hints in previously published phylogenetic trees from mitochondrial genome, nuclear rRNA, from combinations of both and morphology that the Australasian Amblyomma or the Australasian Amblyomma plus the Amblyomma species from the southern cone of South America, might be sister-group to the Amblyomma of the rest of the world. However, a stable phylogenetic framework of Amblyomma for a better understanding of the biogeographic patterns underpinning its diversification is lacking. We used genomic techniques to sequence complete and nearly complete mitochondrial genomes -ca. 15 kbp- as well as the nuclear ribosomal cluster -ca. 8 kbp- for 17 Amblyomma ticks in order to study the phylogeny and biogeographic pattern of the genus Amblyomma, with particular emphasis on the Neotropical region. The new genomic information generated here together with genomic information available on 43 ticks (22 other Amblyomma species and 21 other hard ticks-as outgroup-) were used to perform probabilistic methods of phylogenetic and biogeographic inferences and time-tree estimation using biogeographic dates. In the present paper, we present the strongest evidence yet that Australasian Amblyomma may indeed be the sister-group to the Amblyomma of the rest of the world (species that occur mainly in the Neotropical and Afrotropical zoogeographic regions). Our results showed that all Amblyomma subgenera (Cernyomma, Anastosiella, Xiphiastor, Adenopleura, Aponomma and Dermiomma) are not monophyletic, except for Walkeriana and Amblyomma. Likewise, our best biogeographic scenario supports the origin of Amblyomma and its posterior diversification in the southern hemisphere at 47.8 and 36.8 Mya, respectively. This diversification could be associated with the end of the connection of Australasia and Neotropical ecoregions by the Antarctic land bridge. Also, the biogeographic analyses let us see the colonization patterns of some neotropical Amblyomma species to the Nearctic. We found strong evidence that the main theater of diversification of Amblyomma was the southern hemisphere, potentially driven by the Antarctic Bridge's intermittent connection in the late Eocene. In addition, the subgeneric classification of Amblyomma lacks evolutionary support. Future studies using denser taxonomic sampling may lead to new findings on the phylogenetic relationships and biogeographic history of Amblyomma genus.

Controlling Cyclic Dienamine Reactivity in Radical tert-Alkylation for Molecular Diversity to Synthesize Multicyclic Compounds Possessing a Quaternary Carbon.

Synthesis of diverse sterically congested molecules from a single important intermediate is one of the ideal synthetic strategies in organic synthesis. In this paper, we found that γ-oxoalkyl substituted cyclohexenone derivatives (OAC) possessing a quaternary carbon are a useful key intermediate to derive both congested fused [5,6] rings and spirocycles. For this purpose, we have established an efficient synthetic method to obtain OAC by tertiary alkylation of β-methylcyclohexenone derivatives using α-bromocarbonyl compounds as a tertiary alkyl source. The key to the success of this reaction is controlling the reactivity of the dienamine intermediate. While there have been many reports on enamine reactions, dienamine reactions have not been well studied. Herein, we report controlling reactivity of dienamines and molecular diversification from OAC.

Pyrrolo[2,1-a]isoquinoline scaffolds for developing anti-cancer agents.

Fused pyrrolo[2,1-a]isoquinolines have emerged as compelling molecules with remarkably potent cytotoxic activity and topoisomerase inhibitors. This comprehensive review delves into the intricate world of this family of compounds, analyzing the natural marine lamellarins known for their diverse and complex chemical structures, exploring structure-activity relationships (SARs), and highlighting their remarkable versatility. The review emphasizes their fundamental role as topoisomerase inhibitors and cytotoxic agents, as well as some crucial aspects of the chemistry of pyrrolo[2,1-a]isoquinolines, exploring synthetic strategies in total synthesis and molecular diversification trends, highlighting their importance in the field of medicinal chemistry and beyond.

C–H borylation: a tool for molecular diversification

Iridium-catalyzed C–H activation and borylation has become as a powerful synthetic tool in the past few decades because of the widespread applicability and versatility of organoboron compounds.

Direct Access to Quinazolines and Pyrimidines from Unprotected Indoles and Pyrroles through Nitrogen Atom Insertion.

Recent advances in single-atom insertion reactions have opened up new synthetic approaches for molecular diversification. Developing innovative strategies to directly transform biologically relevant molecules, without any prefunctionalization, is key to further expanding the scope and utility of such transformations. Herein, the direct access to quinazolines and pyrimidines from the corresponding unprotected 1H-indoles and 1H-pyrroles is reported, relying on the implementation of lithium bis(trimethylsilyl)amide (LiHMDS) as a novel nitrogen atom source in combination with commercially available hypervalent iodine reagents. Further application of this strategy in late-stage settings demonstrates its potential in lead structure diversification campaigns.

Domain Architecture Based Methods for Comparative Functional Genomics Toward Therapeutic Drug Target Discovery.

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.

Molecular evolution, diversification, and expression assessment of MADS gene family in Setaria italica, Setaria viridis, and Panicum virgatum.

This paper sheds light on the evolution and expression patterns of MADS genes in Setaria and Panicum virgatum. SiMADS51 and SiMADS64 maybe involved in the ABA-dependent pathway of drought response. The MADS gene family is a key regulatory factor family that controls growth, reproduction, and response to abiotic stress in plants. However, the molecular evolution of this family is rarely reported. Here, a total of 265 MADS genes were identified in Setaria italica (foxtail millet), Setaria viridis (green millet), and Panicum virgatum (switchgrass) and analyzed by bioinformatics, including physicochemical characteristics, subcellular localization, chromosomal position and duplicate, motif distribution, genetic structure, genetic evolvement, and expression patterns. Phylogenetic analysis was used to categorize these genes into M and MIKC types. The distribution of motifs and gene structure were similar for the corresponding types. According to a collinearity study, the MADS genes have been mostly conserved during evolution. The principal cause of their expansion is segmental duplication. However, the MADS gene family tends to shrink in foxtail millet, green millet, and switchgrass. The MADS genes were subjected to purifying selection, but several positive selection sites were also identified in three species. And most of the promoters of MADS genes contain cis-elements related to stress and hormonal response. RNA-seq and quantitative Real-time PCR (qRT-PCR) analysis also were examined. SiMADS genes expression levels are considerably changed in reaction to various treatments, following qRT-PCR analysis. This sheds fresh light on the evolution and expansion of the MADS family in foxtail millet, green millet, and switchgrass, and lays the foundation for further research on their functions.

The Satellite DNAs Populating the Genome of Trigona hyalinata and the Sharing of a Highly Abundant satDNA in Trigona Genus.

Among Meliponini species, c-heterochromatin can occupy large portions of chromosomes. This characteristic could be useful for understanding evolutionary patterns of satellite DNAs (satDNAs), although few sequences have been characterized in these bees. In Trigona, phylogenetically represented by clades A and B, the c-heterochromatin is mostly located in one chromosome arm. Here we used different techniques, including restriction endonucleases and genome sequencing followed by chromosomal analysis, to identify satDNAs that may be contributing to the evolution of c-heterochromatin in Trigona. Our results revealed a highly abundant ThyaSat01-301 satDNA, corresponding to about 13.77% of the Trigona hyalinata genome. Another seven satDNAs were identified, one corresponding to 2.24%, and the other six corresponding to 0.545% of the genome. The satDNA ThyaSat01-301 was shown to be one of the main constituents of the c-heterochromatin of this species, as well as of other species belonging to clade B of Trigona. However, this satDNA was not observed on the chromosomes of species from clade A, demonstrating that the c-heterochromatin is evolving divergently between species of clade A and B, as a consequence of the evolution of repetitive DNA sequences. Finally, our data suggest the molecular diversification of the karyotypes, despite a conservated macrochromosomal structure on the genus.

Correction: Revised molecular phylogeny, global biogeography, and diversification of palms subfamily Coryphoideae (Arecaceae) based on low copy nuclear and plastid regions

Correction: Revised molecular phylogeny, global biogeography, and diversification of palms subfamily Coryphoideae (Arecaceae) based on low copy nuclear and plastid regions

Site-selective post-modification of short α/γ hybrid foldamers: a powerful approach for molecular diversification towards biomedical applications.

The extensive research work in the exhilarating area of foldamers (artificial oligomers possessing well-defined conformation in solution) has shown them to be promising candidates in biomedical research and materials science. The post-modification approach is successful in peptides, proteins, and polymers to modulate their functions. To the best of our knowledge, site-selective post-modification of a foldamer affording molecules with different pendant functional groups within a molecular scaffold has not yet been reported. We demonstrate for the first time that late-stage site-selective functionalization of short hybrid oligomers is an efficient approach to afford molecules with diverse functional groups. In this article, we report the design and synthesis of hybrid peptides with repeating units of leucine (Leu) and 5-amino salicylic acid (ASA), regioselective post-modification, conformational analyses (based on solution-state NMR, circular dichroism and computational studies) and morphological studies of the peptide nanostructures. As a proof-of-concept, we demonstrate the applications of differently modified peptides as drug delivery agents, imaging probes, and anticancer agents. The novel feature of the work is that the difference in reactivity of two phenolic OH groups in short biomimetic peptides was utilized to achieve site-selective post-modification. It is challenging to apply the same approach to short α-peptides having a poor folding tendency, and their post-functionalization may considerably affect their conformation.

Multistep diversification in spatiotemporal bacterial-phage coevolution

The evolutionary arms race between phages and bacteria, where bacteria evolve resistance to phages and phages retaliate with resistance-countering mutations, is a major driving force of molecular innovation and genetic diversification. Yet attempting to reproduce such ongoing retaliation dynamics in the lab has been challenging; laboratory coevolution experiments of phage and bacteria are typically performed in well-mixed environments and often lead to rapid stagnation with little genetic variability. Here, co-culturing motile E. coli with the lytic bacteriophage T7 on swimming plates, we observe complex spatiotemporal dynamics with multiple genetically diversifying adaptive cycles. Systematically quantifying over 10,000 resistance-infectivity phenotypes between evolved bacteria and phage isolates, we observe diversification into multiple coexisting ecotypes showing a complex interaction network with both host-range expansion and host-switch tradeoffs. Whole-genome sequencing of these evolved phage and bacterial isolates revealed a rich set of adaptive mutations in multiple genetic pathways including in genes not previously linked with phage-bacteria interactions. Synthetically reconstructing these new mutations, we discover phage-general and phage-specific resistance phenotypes as well as a strong synergy with the more classically known phage-resistance mutations. These results highlight the importance of spatial structure and migration for driving phage-bacteria coevolution, providing a concrete system for revealing new molecular mechanisms across diverse phage-bacterial systems.

Revised molecular phylogeny, global biogeography, and diversification of palms subfamily Coryphoideae (Arecaceae) based on low copy nuclear and plastid regions.

Coryphoideae are palmate-leaved palms from the family Arecaceae consisting of 46 genera representing 421 species. Although several phylogenetic analyses based on different genomic regions have been carried out on Coryphoideae, a fully resolved molecular phylogenetic tree has not been reported yet. To achieve this, we applied two phylogenetic reconstruction methods: Maximum Likelihood and Bayesian Inference, using amplified sampling by retrieving chloroplast and nuclear DNA sequences from NCBI and adding newly produced sequences from Indian accession into the dataset. The same dataset (chloroplast + nuclear DNA sequences) was used to estimate divergence times and the evolutionary history of Coryphoideae with a Bayesian uncorrelated, lognormal relaxed-clock approach and a Statistical Divergence-Vicariance Analysis method,respectively. The phylogenetic analyses based on a combined chloroplast and nuclear DNA sequence dataset showed well-resolved relationships within the subfamily. Both phylogenetic trees divide Coryphoideae into two main groups: CSPT (Crysophileae, Sabaleae, Phoeniceae, and Trachycarpeae) and the Syncarpous group. These main groups are segregated into eight tribes (Trachycarpeae, Phoeniceae, Sabaleae, Crysophileae, Borasseae, Corypheae, Caryoteae, and Chuniophoeniceae) and four subtribes (Rhapidine, Livistoninae, Hyphaeninae, and Lataniinae) with strong support-values. Most previously unresolved and doubtful relationships within tribes Trachycarpeae and Crysophilieae are now resolved and well-supported. The reconstructed phylogenetic trees support all previous systematic revisions of the subfamily. All Indian sampled species of Arenga, Bentinckia, Hyphaene, and Trachycarpus show close relation with their respective congeneric species. Molecular dating results and integration of biogeography suggest that Coryphoideae originated in Laurasia at ~95.12Ma and then diverged into the tropical and subtropical regions of the whole world. This study offers the correct combination of nuclear and plastid regions to test the current and future systematic revisions.

Nickel-Catalyzed Cross-Electrophile 1,2-Silyl-Arylation of 1,3-Dienes with Chlorosilanes and Aryl Bromides.

Catalytic, three-component, cross-electrophile reactions have recently emerged as a promising tool for molecular diversification, but studies have focused mainly on the alkyl-carbonations of alkenes. Herein, the scope of this method has been extended to conjugated dienes and silicon chemistry through silylative difunctionalization of 1,3-dienes with chlorosilanes and aryl bromides. The reaction proceeds under mild conditions to afford 1,2-linear-silylated products, a selectivity that is different to those obtained from conventional methods via an intermediary of H(C)-η3 -π-allylmetal species. Preliminary mechanistic studies reveal that chlorosilane reacts with 1,3-diene first and then couples with aryl bromide.

Nickel‐Catalyzed Cross‐Electrophile 1,2‐Silyl‐Arylation of 1,3‐Dienes with Chlorosilanes and Aryl Bromides

AbstractCatalytic, three‐component, cross‐electrophile reactions have recently emerged as a promising tool for molecular diversification, but studies have focused mainly on the alkyl‐carbonations of alkenes. Herein, the scope of this method has been extended to conjugated dienes and silicon chemistry through silylative difunctionalization of 1,3‐dienes with chlorosilanes and aryl bromides. The reaction proceeds under mild conditions to afford 1,2‐linear‐silylated products, a selectivity that is different to those obtained from conventional methods via an intermediary of H(C)‐η3‐π‐allylmetal species. Preliminary mechanistic studies reveal that chlorosilane reacts with 1,3‐diene first and then couples with aryl bromide.

Rapid molecular diversification and homogenization of clustered major ampullate silk genes in Argiope garden spiders.

The evolutionary diversification of orb-web weaving spiders is closely tied to the mechanical performance of dragline silk. This proteinaceous fiber provides the primary structural framework of orb web architecture, and its extraordinary toughness allows these structures to absorb the high energy of aerial prey impact. The dominant model of dragline silk molecular structure involves the combined function of two highly repetitive, spider-specific, silk genes (spidroins)-MaSp1 and MaSp2. Recent genomic studies, however, have suggested this framework is overly simplistic, and our understanding of how MaSp genes evolve is limited. Here we present a comprehensive analysis of MaSp structural and evolutionary diversity across species of Argiope (garden spiders). This genomic analysis reveals the largest catalog of MaSp genes found in any spider, driven largely by an expansion of MaSp2 genes. The rapid diversification of Argiope MaSp genes, located primarily in a single genomic cluster, is associated with profound changes in silk gene structure. MaSp2 genes, in particular, have evolved complex hierarchically organized repeat units (ensemble repeats) delineated by novel introns that exhibit remarkable evolutionary dynamics. These repetitive introns have arisen independently within the genus, are highly homogenized within a gene, but diverge rapidly between genes. In some cases, these iterated introns are organized in an alternating structure in which every other intron is nearly identical in sequence. We hypothesize that this intron structure has evolved to facilitate homogenization of the coding sequence. We also find evidence of intergenic gene conversion and identify a more diverse array of stereotypical amino acid repeats than previously recognized. Overall, the extreme diversification found among MaSp genes requires changes in the structure-function model of dragline silk performance that focuses on the differential use and interaction among various MaSp paralogs as well as the impact of ensemble repeat structure and different amino acid motifs on mechanical behavior.

A special issue of Essays in Biochemistry on evolutionary developmental biology.

Evolutionary developmental biology (or evo devo) is a broad field that aims to understand how developmental processes evolve and how this underpins phenotypic change and organismal diversification. This encompasses a need to understand theoretical concepts in evolutionary biology and how tissues, cells, genes, proteins and regulatory elements function and evolve. The articles in this special issue review key topics in the field of evo devo including advances in theory and methodology as well as our latest knowledge about molecular, cellular and organismal functionality and diversification.