Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.315
Filtrar
1.
Nucleic Acids Res ; 48(4): 1607-1626, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31984425

RESUMO

7-Methylguanosine 5' cap on mRNA is necessary for efficient protein expression in vitro and in vivo. Recent studies revealed structural diversity of endogenous mRNA caps, which carry different 5'-terminal nucleotides and additional methylations (2'-O-methylation and m6A). Currently available 5'-capping methods do not address this diversity. We report trinucleotide 5' cap analogs (m7GpppN(m)pG), which are utilized by RNA polymerase T7 to initiate transcription from templates carrying Φ6.5 promoter and enable production of mRNAs differing in the identity of the first transcribed nucleotide (N = A, m6A, G, C, U) and its methylation status (±2'-O-methylation). HPLC-purified mRNAs carrying these 5' caps were used to study protein expression in three mammalian cell lines (3T3-L1, HeLa and JAWS II). The highest expression was observed for mRNAs carrying 5'-terminal A/Am and m6Am, whereas the lowest was observed for G and Gm. The mRNAs carrying 2'-O-methyl at the first transcribed nucleotide (cap 1) had significantly higher expression than unmethylated counterparts (cap 0) only in JAWS II dendritic cells. Further experiments indicated that the mRNA expression characteristic does not correlate with affinity for translation initiation factor 4E or in vitro susceptibility to decapping, but instead depends on mRNA purity and the immune state of the cells.


Assuntos
Biossíntese de Proteínas/genética , Capuzes de RNA/genética , RNA Mensageiro/isolamento & purificação , Transcrição Genética , Animais , Eucariotos/genética , Fator de Iniciação 4E em Eucariotos/genética , Regulação da Expressão Gênica/genética , Células HeLa , Humanos , Metilação , Nucleotídeos/genética , Processamento de Proteína Pós-Traducional/genética , RNA Mensageiro/genética
2.
Nat Commun ; 11(1): 540, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992709

RESUMO

Eukaryotic transcription factors (TF) function by binding to short 6-10 bp DNA recognition sites located near their target genes, which are scattered through vast genomes. Such process surmounts enormous specificity, efficiency and celerity challenges using a molecular mechanism that remains poorly understood. Combining biophysical experiments, theory and bioinformatics, we dissect the interplay between the DNA-binding domain of Engrailed, a Drosophila TF, and the regulatory regions of its target genes. We find that Engrailed binding affinity is strongly amplified by the DNA regions flanking the recognition site, which contain long tracts of degenerate recognition-site repeats. Such DNA organization operates as an antenna that attracts TF molecules in a promiscuous exchange among myriads of intermediate affinity binding sites. The antenna ensures a local TF supply, enables gene tracking and fine control of the target site's basal occupancy. This mechanism illuminates puzzling gene expression data and suggests novel engineering strategies to control gene expression.


Assuntos
Sítios de Ligação , DNA/metabolismo , Proteínas de Drosophila/metabolismo , Eucariotos/genética , Regulação da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição/metabolismo , Animais , Sequência de Bases , Fenômenos Biofísicos , Biologia Computacional , Proteínas de Ligação a DNA , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Genoma , Cinética , Modelos Teóricos , Conformação Molecular , Termodinâmica
3.
Gene ; 726: 144155, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31629821

RESUMO

Histones are genes that regulate chromatin structure. They are present in both eukaryotes and archaea, and form nucleosomes with DNA, but their exact evolutionary origins have hitherto remained a mystery. A longstanding hypothesis is that they have precursors in ribosomal proteins with whom they share much in common in terms of size and chemistry. By examining the proteome of the Asgard archaeon, Lokiarchaeum, the most conserved of all the histones, H4, is found to plausibly be homologous with one of its 30S ribosomal proteins, RPS6. This is based on both sequence identity and statistical analysis. The N-terminal tail, containing key sites involved in post-translational modifications, is notably present in the precursor gene. Although other archaeal groups possess similar homologs, these are not as close to H4 as the one found in Lokiarchaeum. The other core histones, H2A, H2B and H3, appear to have also evolved from the same ribosomal protein. Parts of H4 are also similar to another ribosomal protein, namely RPS15, suggesting that the ancestral precursor could have resembled both. Eukaryotic histones, in addition, appear to have an independent origin to that of their archaeal counterparts that evolved from similar, but still different, 30S subunit proteins, some of which are much more like histones in terms of their physical structure. The nucleosome may, therefore, be not only of archaeal but also of ribosomal origin.


Assuntos
Cromatina/genética , Histonas/genética , Proteínas Ribossômicas/genética , Archaea/genética , DNA/genética , Eucariotos/genética , Evolução Molecular , Nucleossomos/genética , Processamento de Proteína Pós-Traducional/genética
4.
Nat Biotechnol ; 37(12): 1466-1470, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792410

RESUMO

Multiple sequence alignments (MSAs) are used for structural1,2 and evolutionary predictions1,2, but the complexity of aligning large datasets requires the use of approximate solutions3, including the progressive algorithm4. Progressive MSA methods start by aligning the most similar sequences and subsequently incorporate the remaining sequences, from leaf to root, based on a guide tree. Their accuracy declines substantially as the number of sequences is scaled up5. We introduce a regressive algorithm that enables MSA of up to 1.4 million sequences on a standard workstation and substantially improves accuracy on datasets larger than 10,000 sequences. Our regressive algorithm works the other way around from the progressive algorithm and begins by aligning the most dissimilar sequences. It uses an efficient divide-and-conquer strategy to run third-party alignment methods in linear time, regardless of their original complexity. Our approach will enable analyses of extremely large genomic datasets such as the recently announced Earth BioGenome Project, which comprises 1.5 million eukaryotic genomes6.


Assuntos
Algoritmos , Alinhamento de Sequência/métodos , Bases de Dados Genéticas , Eucariotos/genética , Genômica/métodos , Análise de Regressão
5.
BMC Evol Biol ; 19(1): 219, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791235

RESUMO

BACKGROUND: Phylogenetic species trees are widely used in inferring evolutionary relationships. Existing software and algorithms mainly focus on phylogenetic inference. However, less attention has been paid to intermediate steps, such as processing extremely large sequences and preparing configure files to connect multiple software. When the species number is large, the intermediate steps become a bottleneck that may seriously affect the efficiency of tree building. RESULTS: Here, we present an easy-to-use pipeline named PhySpeTree to facilitate the reconstruction of species trees across bacterial, archaeal, and eukaryotic organisms. Users need only to input the abbreviations of species names; PhySpeTree prepares complex configure files for different software, then automatically downloads genomic data, cleans sequences, and builds trees. PhySpeTree allows users to perform critical steps such as sequence alignment and tree construction by adjusting advanced options. PhySpeTree provides two parallel pipelines based on concatenated highly conserved proteins and small subunit ribosomal RNA sequences, respectively. Accessory modules, such as those for inserting new species, generating visualization configurations, and combining trees, are distributed along with PhySpeTree. CONCLUSIONS: Together with accessory modules, PhySpeTree significantly simplifies tree reconstruction. PhySpeTree is implemented in Python running on modern operating systems (Linux, macOS, and Windows). The source code is freely available with detailed documentation (https://github.com/yangfangs/physpetools).


Assuntos
Filogenia , Software , Algoritmos , Archaea/classificação , Archaea/genética , Bactérias/classificação , Bactérias/genética , Sequência de Bases , Evolução Biológica , Eucariotos/classificação , Eucariotos/genética , Genômica , RNA Ribossômico/genética , Alinhamento de Sequência
6.
BMC Evol Biol ; 19(1): 224, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818253

RESUMO

BACKGROUND: Eukaryotes acquired the trait of oxygenic photosynthesis through endosymbiosis of the cyanobacterial progenitor of plastid organelles. Despite recent advances in the phylogenomics of Cyanobacteria, the phylogenetic root of plastids remains controversial. Although a single origin of plastids by endosymbiosis is broadly supported, recent phylogenomic studies are contradictory on whether plastids branch early or late within Cyanobacteria. One underlying cause may be poor fit of evolutionary models to complex phylogenomic data. RESULTS: Using Posterior Predictive Analysis, we show that recently applied evolutionary models poorly fit three phylogenomic datasets curated from cyanobacteria and plastid genomes because of heterogeneities in both substitution processes across sites and of compositions across lineages. To circumvent these sources of bias, we developed CYANO-MLP, a machine learning algorithm that consistently and accurately phylogenetically classifies ("phyloclassifies") cyanobacterial genomes to their clade of origin based on bioinformatically predicted function-informative features in tRNA gene complements. Classification of cyanobacterial genomes with CYANO-MLP is accurate and robust to deletion of clades, unbalanced sampling, and compositional heterogeneity in input tRNA data. CYANO-MLP consistently classifies plastid genomes into a late-branching cyanobacterial sub-clade containing single-cell, starch-producing, nitrogen-fixing ecotypes, consistent with metabolic and gene transfer data. CONCLUSIONS: Phylogenomic data of cyanobacteria and plastids exhibit both site-process heterogeneities and compositional heterogeneities across lineages. These aspects of the data require careful modeling to avoid bias in phylogenomic estimation. Furthermore, we show that amino acid recoding strategies may be insufficient to mitigate bias from compositional heterogeneities. However, the combination of our novel tRNA-specific strategy with machine learning in CYANO-MLP appears robust to these sources of bias with high accuracy in phyloclassification of cyanobacterial genomes. CYANO-MLP consistently classifies plastids as late-branching Cyanobacteria, consistent with independent evidence from signature-based approaches and some previous phylogenetic studies.


Assuntos
Cianobactérias/genética , Eucariotos/citologia , Eucariotos/genética , Plastídeos/genética , Evolução Biológica , Modelos Biológicos , Fotossíntese , Filogenia , RNA de Transferência , Simbiose
7.
Mol Biol (Mosk) ; 53(6): 933-953, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31876274

RESUMO

Chromatin packing in eukaryotic chromosomes has been traditionally viewed as a hierarchical process, in which nucleosome chains fold into helical chromatin fibers. These fibers would then fold into more complex regular structures. However, recent chromatin imaging studies and analyses of chromosomal DNA contacts within the 3D space of the cell nucleus have necessitated a radical revision of the hierarchical chromatin packing model. According to the new studies, the nucleosome chain has a free spatial configuration without regular helical fibers in most cell types. The overall 3D organization of DNA in the cell nucleus includes chromatin loops and contact domains of up to several million base pairs in size. During cell differentiation, individual structure-functional chromatin domains marked by similar types of histone modifications and functional states can merge together and form chromosomal subcompartments suited for local gene activation or repression. This "attraction of likenesses" may be mediated by direct self-association of nucleosome chains as well as by architectural chromatin proteins making oligomeric protein "bridges" between nucleosomes as well as larger dynamic condensates leading to liquid-liquid phase separation inside the cell nucleus. Future studies of mechanisms of chromatin self-association and compartmentalization will require a combination of molecular, imaging, and computational approaches capable of revealing the 3D organization of the eukaryotic genome with nucleosomal resolution.


Assuntos
Cromatina/química , Cromatina/metabolismo , Posicionamento Cromossômico , Eucariotos/genética , DNA/química , DNA/metabolismo , Eucariotos/citologia , Histonas/química , Histonas/metabolismo , Nucleossomos/química , Nucleossomos/metabolismo
8.
Int J Mol Sci ; 21(1)2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31861340

RESUMO

The p53 family of transcription factors plays key roles in development, genome stability, senescence and tumor development, and p53 is the most important tumor suppressor protein in humans. Although intensively investigated for many years, its initial evolutionary history is not yet fully elucidated. Using bioinformatic and structure prediction methods on current databases containing newly-sequenced genomes and transcriptomes, we present a detailed characterization of p53 family homologs in remote members of the Holozoa group, in the unicellular clades Filasterea, Ichthyosporea and Corallochytrea. Moreover, we show that these newly characterized homologous sequences contain domains that can form structures with high similarity to the human p53 family DNA-binding domain, and some also show similarities to the oligomerization and SAM domains. The presence of these remote homologs demonstrates an ancient origin of the p53 protein family.


Assuntos
Eucariotos/genética , Evolução Molecular , Família Multigênica , Homologia de Sequência de Aminoácidos , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Sequência de Aminoácidos , Bases de Dados Genéticas , Eucariotos/classificação , Éxons , Íntrons , Modelos Moleculares , Filogenia , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteína Supressora de Tumor p53/metabolismo
9.
PLoS Genet ; 15(11): e1008404, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31774811

RESUMO

Interspecific hybridization is the process where closely related species mate and produce offspring with admixed genomes. The genomic revolution has shown that hybridization is common, and that it may represent an important source of novel variation. Although most interspecific hybrids are sterile or less fit than their parents, some may survive and reproduce, enabling the transfer of adaptive variants across the species boundary, and even result in the formation of novel evolutionary lineages. There are two main variants of hybrid species genomes: allopolyploid, which have one full chromosome set from each parent species, and homoploid, which are a mosaic of the parent species genomes with no increase in chromosome number. The establishment of hybrid species requires the development of reproductive isolation against parental species. Allopolyploid species often have strong intrinsic reproductive barriers due to differences in chromosome number, and homoploid hybrids can become reproductively isolated from the parent species through assortment of genetic incompatibilities. However, both types of hybrids can become further reproductively isolated, gaining extrinsic isolation barriers, by exploiting novel ecological niches, relative to their parents. Hybrids represent the merging of divergent genomes and thus face problems arising from incompatible combinations of genes. Thus hybrid genomes are highly dynamic and undergo rapid evolutionary change, including genome stabilization in which selection against incompatible combinations results in fixation of compatible ancestry block combinations within the hybrid species. The potential for rapid adaptation or speciation makes hybrid genomes a particularly exciting subject of in evolutionary biology. Here we summarize how introgressed alleles or hybrid species can establish and how the resulting hybrid genomes evolve.


Assuntos
Evolução Biológica , Eucariotos/genética , Genoma/genética , Hibridização de Ácido Nucleico/genética , Ecossistema , Especiação Genética , Genoma de Planta/genética , Genômica , Isolamento Reprodutivo
10.
BMC Bioinformatics ; 20(1): 558, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703556

RESUMO

BACKGROUND: Vast amounts of next generation sequencing RNA data has been deposited in archives, accompanying very diverse original studies. The data is readily available also for other purposes such as genome annotation or transcriptome assembly. However, selecting a subset of available experiments, sequencing runs and reads for this purpose is a nontrivial task and complicated by the inhomogeneity of the data. RESULTS: This article presents the software VARUS that selects, downloads and aligns reads from NCBI's Sequence Read Archive, given only the species' binomial name and genome. VARUS automatically chooses runs from among all archived runs to randomly select subsets of reads. The objective of its online algorithm is to cover a large number of transcripts adequately when network bandwidth and computing resources are limited. For most tested species VARUS achieved both a higher sensitivity and specificity with a lower number of downloaded reads than when runs were manually selected. At the example of twelve eukaryotic genomes, we show that RNA-Seq that was sampled with VARUS is well-suited for fully-automatic genome annotation with BRAKER. CONCLUSIONS: With VARUS, genome annotation can be automatized to the extent that not even the selection and quality control of RNA-Seq has to be done manually. This introduces the possibility to have fully automatized genome annotation loops over potentially many species without incurring a loss of accuracy over a manually supervised annotation process.


Assuntos
Bases de Dados Genéticas , RNA Complementar/genética , Análise de Sequência de RNA/métodos , Software , Algoritmos , Animais , Drosophila melanogaster/genética , Eucariotos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Íntrons/genética , Anotação de Sequência Molecular , Transcriptoma/genética
11.
J Microbiol ; 57(11): 1003-1011, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31555993

RESUMO

while several methods for determining postmortem submersion interval (PMSI) in drowning cases have been suggested, the estimation of PMSI remains difficult. Next-generation sequencing (NGS) technology enables simultaneous identification of multiple taxa from environmental samples. Although NGS has been applied to estimate time since death, this application has been mainly focused on terrestrial cases. As a case study, we investigated microeukaryotic biodiversity and community structures in submerged car bonnet and drowned pig using NGS technology. NGS analysis showed that the microeukaryotic biodiversity in pig carcass was relevantly lower than that in car bonnet. NGS results also revealed that water molds and algae were related to decomposition. Relative abundances of Filobasidium, Achlya, Saprolegnia, Hydrodicton, Lobosphaera, and Scenedesmus varied with decomposition period. This data indicated that these taxa might be useful as good indicators to estimate PMSI. This study showed microeukaryotic community analysis using NGS technology may help solve drowning cases in forensic investigation.


Assuntos
Afogamento/diagnóstico , Eucariotos/classificação , Medicina Legal/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mudanças Depois da Morte , Animais , Biodiversidade , DNA/isolamento & purificação , Eucariotos/genética , Eucariotos/isolamento & purificação , República da Coreia , Suínos , Fatores de Tempo
12.
Integr Comp Biol ; 59(4): 856-863, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504533

RESUMO

Eukaryotes are the outcome of an ancient symbiosis and as such, eukaryotic cells fundamentally possess two genomes. As a consequence, gene products encoded by both nuclear and mitochondrial genomes must interact in an intimate and precise fashion to enable aerobic respiration in eukaryotes. This genomic architecture of eukaryotes is proposed to necessitate perpetual coevolution between the nuclear and mitochondrial genomes to maintain coadaptation, but the presence of two genomes also creates the opportunity for intracellular conflict. In the collection of papers that constitute this symposium volume, scientists working in diverse organismal systems spanning vast biological scales address emerging topics in integrative, comparative biology in light of mitonuclear interactions.


Assuntos
Coevolução Biológica , Núcleo Celular/fisiologia , Eucariotos/fisiologia , Genoma Mitocondrial/fisiologia , Adaptação Biológica , Núcleo Celular/genética , Eucariotos/genética , Genoma Mitocondrial/genética
13.
PLoS Negl Trop Dis ; 13(9): e0007444, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31490933

RESUMO

Visceral leishmaniasis (VL) caused by Leishmania donovani remains of public health concern in rural India. Those at risk of VL are also at risk of other neglected tropical diseases (NTDs) including soil transmitted helminths. Intestinal helminths are potent regulators of host immune responses sometimes mediated through cross-talk with gut microbiota. We evaluate a meta-taxonomic approach to determine the composition of prokaryotic and eukaryotic gut microflora using amplicon-based sequencing of 16S ribosomal RNA (16S rRNA) and 18S rRNA gene regions. The most abundant bacterial taxa identified in faecal samples from Bihar State India were Prevotella (37.1%), Faecalibacterium (11.3%), Escherichia-Shigella (9.1%), Alloprevotella (4.5%), Bacteroides (4.1%), Ruminococcaceae UCG-002 (1.6%), and Bifidobacterium (1.5%). Eukaryotic taxa identified (excluding plant genera) included Blastocystis (57.9%; Order: Stramenopiles), Dientamoeba (12.1%; Family: Tritrichomonadea), Pentatrichomonas (10.1%; Family: Trichomonodea), Entamoeba (3.5%; Family: Entamoebida), Ascaridida (0.8%; Family: Chromodorea; concordant with Ascaris by microscopy), Rhabditida (0.8%; Family: Chromodorea; concordant with Strongyloides), and Cyclophyllidea (0.2%; Order: Eucestoda; concordant with Hymenolepis). Overall alpha (Shannon's, Faith's and Pielou's indices) and beta (Bray-Curtis dissimilarity statistic; weighted UniFrac distances) diversity of taxa did not differ significantly by age, sex, geographic subdistrict, or VL case (N = 23) versus endemic control (EC; N = 23) status. However, taxon-specific associations occurred: (i) Ruminococcaceae UCG- 014 and Gastranaerophilales_uncultured bacterium were enriched in EC compared to VL cases; (ii) Pentatrichomonas was more abundant in VL cases than in EC, whereas the reverse occurred for Entamoeba. Across the cohort, high Escherichia-Shigella was associated with reduced bacterial diversity, while high Blastocystis was associated with high bacterial diversity and low Escherichia-Shigella. Individuals with high Blastocystis had low Bacteroidaceae and high Clostridiales vadin BB60 whereas the reverse held true for low Blastocystis. This scoping study provides useful baseline data upon which to develop a broader analysis of pathogenic enteric microflora and their influence on gut microbial health and NTDs generally.


Assuntos
Bactérias/isolamento & purificação , Eucariotos/isolamento & purificação , Fezes/microbiologia , Fezes/parasitologia , Leishmaniose Visceral/microbiologia , Leishmaniose Visceral/parasitologia , Adolescente , Adulto , Bactérias/classificação , Bactérias/genética , Criança , Pré-Escolar , Estudos de Coortes , Eucariotos/classificação , Eucariotos/genética , Feminino , Microbioma Gastrointestinal , Humanos , Índia/epidemiologia , Leishmania donovani/fisiologia , Masculino , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Adulto Jovem
14.
Genes Dev ; 33(17-18): 1098-1116, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31481535

RESUMO

Transposable elements (TEs) are mobile DNA sequences that colonize genomes and threaten genome integrity. As a result, several mechanisms appear to have emerged during eukaryotic evolution to suppress TE activity. However, TEs are ubiquitous and account for a prominent fraction of most eukaryotic genomes. We argue that the evolutionary success of TEs cannot be explained solely by evasion from host control mechanisms. Rather, some TEs have evolved commensal and even mutualistic strategies that mitigate the cost of their propagation. These coevolutionary processes promote the emergence of complex cellular activities, which in turn pave the way for cooption of TE sequences for organismal function.


Assuntos
Evolução Biológica , Elementos de DNA Transponíveis/fisiologia , Eucariotos/fisiologia , Interações Hospedeiro-Patógeno/fisiologia , Adaptação Fisiológica/genética , Animais , Elementos de DNA Transponíveis/genética , Eucariotos/genética , Genoma/genética , Humanos
15.
PLoS Genet ; 15(9): e1008386, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31527909

RESUMO

Errors throughout gene expression are likely deleterious, hence genomes are under selection to ameliorate their consequences. Additional stop codons (ASCs) are in-frame nonsense 'codons' downstream of the primary stop which may be read by translational machinery should the primary stop have been accidentally read through. Prior evidence in several eukaryotes suggests that ASCs are selected to prevent potentially-deleterious consequences of read-through. We extend this evidence showing that enrichment of ASCs is common but not universal for single cell eukaryotes. By contrast, there is limited evidence as to whether the same is true in other taxa. Here, we provide the first systematic test of the hypothesis that ASCs act as a fail-safe mechanism in eubacteria, a group with high read-through rates. Contra to the predictions of the hypothesis we find: there is paucity, not enrichment, of ASCs downstream; substitutions that degrade stops are more frequent in-frame than out-of-frame in 3' sequence; highly expressed genes are no more likely to have ASCs than lowly expressed genes; usage of the leakiest primary stop (TGA) in highly expressed genes does not predict ASC enrichment even compared to usage of non-leaky stops (TAA) in lowly expressed genes, beyond downstream codon +1. Any effect at the codon immediately proximal to the primary stop can be accounted for by a preference for a T/U residue immediately following the stop, although if anything, TT- and TC- starting codons are preferred. We conclude that there is no compelling evidence for ASC selection in eubacteria. This presents an unusual case in which the same error could be solved by the same mechanism in eukaryotes and prokaryotes but is not. We discuss two possible explanations: that, owing to the absence of nonsense mediated decay, bacteria may solve read-through via gene truncation and in eukaryotes certain prion states cause raised read-through rates.


Assuntos
Regiões 3' não Traduzidas/genética , Bactérias/genética , Códon de Terminação/genética , Códon sem Sentido/genética , Eucariotos/genética , Evolução Molecular , Expressão Gênica/genética , Genoma , Degradação do RNAm Mediada por Códon sem Sentido/genética , Fases de Leitura Aberta/genética
16.
Biochemistry (Mosc) ; 84(8): 870-883, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31522669

RESUMO

It has been suggested that RNA polymerase ribozyme displaying reverse transcriptase and integrase activities has played a vital role in the origin of life on Earth. Here, we present a hypothesis that formation of universal ancestral units of all living organisms - retroelements - in the evolution was mediated by reverse transcriptase. The propensity of retroelements to mutations and their insertion capacity have formed a basis for the origin of complex DNA structures - primary genomes - that have given rise to archaea, eukaryotes, bacteria, and viruses. Conserved properties of retroelements have been preserved throughout the evolution; their modifications have facilitated the emergence of mechanisms for the interactions between proteins and nucleic acids. Life has evolved due to insertional mutagenesis and competition of autonomously replicating polynucleotides that allowed to preserve structures with adaptive properties. We hypothesize that natural selection of mechanisms for the defense against insertions based on the ribonuclease activity of reverse transcriptase ribozyme has led to the emergence of all universal enzymatic systems for the processing of RNA molecules. These systems have been and still remain the key sources of structural and functional transformations of genomes in the course of evolution. The data presented in this review suggest that the process of translation, which unifies the nucleic acid and protein worlds, has developed as a modification of the defense mechanisms against insertions. Polypeptides formed by this defense system have potentiated the activity of ribozymes in the composition of ribonucleoproteins (RNPs) and even functionally replaced them as more efficient catalysts of biological reactions. Here, we analyze the mechanisms of retroelement involvement in the structural and regulatory transformations of eukaryotic genomes supposedly reflecting the adaptive principles that had originated during the beginning of life on Earth. Simultaneously with the evolution of existing proteins, retroelements have served as sources of new ribozymes, such as long non-coding RNAs. These ribozymes can function in complexes with proteins in the composition of RNPs, as well as display independent catalytic and translational activities; their genes have a potential for the transformation into protein-coding genes. Hence, the conserved principles of RNA, DNA, and proteins interregulation formed at the time of life origin on Earth have been used throughout the evolution.


Assuntos
Evolução Molecular , Origem da Vida , DNA Polimerase Dirigida por RNA/fisiologia , Animais , Elementos de DNA Transponíveis/genética , RNA Polimerases Dirigidas por DNA , Escherichia coli/enzimologia , Escherichia coli/genética , Eucariotos/genética , Humanos , Íntrons/genética , Biossíntese de Proteínas , RNA Catalítico/fisiologia , RNA Longo não Codificante/genética , RNA de Transferência/genética , RNA de Transferência/metabolismo , Retroelementos
17.
Int J Mol Sci ; 20(15)2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390737

RESUMO

Alternative splicing of pre-mRNAs is a crucial mechanism for maintaining protein diversity in eukaryotes without requiring a considerable increase of genes in the number. Due to rapid advances in high-throughput sequencing technologies and computational algorithms, it is anticipated that alternative splicing events will be more intensively studied to address different kinds of biological questions. The occurrences of alternative splicing mean that all exons could be classified to be either constitutively or alternatively spliced depending on whether they are virtually included into all mature mRNAs. From an evolutionary point of view, therefore, the alternatively spliced exons would have been associated with distinctive biological characteristics in comparison with constitutively spliced exons. In this paper, we first outline the representative types of alternative splicing events and exon classification, and then review sequence and evolutionary features for the alternatively spliced exons. The main purpose is to facilitate understanding of the biological implications of alternative splicing in eukaryotes. This knowledge is also helpful to establish computational approaches for predicting the splicing pattern of exons.


Assuntos
Processamento Alternativo , Eucariotos/genética , Evolução Molecular , Éxons , Animais , Regulação da Expressão Gênica , Humanos , Íntrons , Análise de Sequência de DNA
18.
J Microbiol ; 57(10): 852-864, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31376109

RESUMO

Recent work suggests that microbial community composition in high-elevation lakes is significantly influenced by microbes entering from upstream terrestrial and aquatic habitats. To test this idea, we conducted 18S and 16S rDNA surveys of microbial communities in a high-alpine lake in the Colorado Rocky Mountains. We compared the microbial community of the lake to water entering the lake and to uphill soils that drain into the lake. Utilizing hydrological and abiotic data, we identified potential factors controlling microbial diversity and community composition. Results show a diverse community entering the lake at the inlet with a strong resemblance to uphill terrestrial and aquatic communities. In contrast, the lake communities (water column and outlet) showed significantly lower diversity and were significantly different from the inlet communities. Assumptions of neutral community assembly poorly predicted community differences between the inlet and lake, whereas "variable selection" and "dispersal limitation" were predicted to dominate. Similarly, the lake communities were correlated with discharge rate, indicating that longer hydraulic residence times limit dispersal, allowing selective pressures within the lake to structure communities. Sulfate and inorganic nitrogen and phosphorus concentrations correlated with community composition, indicating "bottom up" controls on lake community assembly. Furthermore, bacterial community composition was correlated with both zooplankton density and eukaryotic community composition, indicating biotic controls such as "top-down" interactions also contribute to community assembly in the lake. Taken together, these community analyses suggest that deterministic biotic and abiotic selection within the lake coupled with dispersal limitation structures the microbial communities in Green Lake 4.


Assuntos
Bactérias/isolamento & purificação , Eucariotos/isolamento & purificação , Lagos/microbiologia , Lagos/parasitologia , Bactérias/classificação , Bactérias/genética , Biodiversidade , Colorado , Eucariotos/classificação , Eucariotos/genética , Lagos/química , Microbiota , Nitrogênio/análise , Nitrogênio/metabolismo , Sulfatos/análise , Sulfatos/metabolismo
19.
Nat Struct Mol Biol ; 26(9): 777-782, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31439942

RESUMO

Transcription regulation is critical to organism development and homeostasis. Control of expression of the 20,000 genes in human cells requires many hundreds of proteins acting through sophisticated multistep mechanisms. In this Historical Perspective, I highlight the progress that has been made in elucidating eukaryotic transcriptional mechanisms through an array of disciplines and approaches, and how this concerted effort has been driven by the development of new technologies.


Assuntos
Bioquímica/história , Bioquímica/métodos , Eucariotos/enzimologia , Eucariotos/genética , Biologia Molecular/história , Biologia Molecular/métodos , Transcrição Genética , História do Século XX , História do Século XXI
20.
Nat Struct Mol Biol ; 26(9): 783-791, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31439941

RESUMO

The landmark 1969 discovery of nuclear RNA polymerases I, II and III in diverse eukaryotes represented a major turning point in the field that, with subsequent elucidation of the distinct structures and functions of these enzymes, catalyzed an avalanche of further studies. In this Review, written from a personal and historical perspective, I highlight foundational biochemical studies that led to the discovery of an expanding universe of the components of the transcriptional and regulatory machineries, and a parallel complexity in gene-specific mechanisms that continue to be explored to the present day.


Assuntos
Bioquímica/história , Eucariotos/enzimologia , Eucariotos/genética , Biologia Molecular/história , Fatores de Transcrição/isolamento & purificação , Fatores de Transcrição/metabolismo , Transcrição Genética , História do Século XX , História do Século XXI
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA