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1.
Gene ; 760: 145020, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32755656

RESUMO

Conserved sequences across species have always provided valuable insights to improve our understanding on the human genome's entity and the interplay among different loci. Lymphoma/leukemia related factor (LRF) is encoded by ZBTB7A gene and belongs to an evolutionarily conserved family of transcription factors, implicated in vital cellular functions. The present data, demonstrating the wide-spread and the high overlap of the LRF/ZBTB7A recognition sites with genomic segments identified as CpG islands in the human genome, suggest that its binding capacity strongly depends on a specific sequence-encoded feature within CpGs. We have previously shown that de-methylation of the CpG island 326 lying in the ZBTB7A gene promoter is associated with impaired pharmacological induction of fetal hemoglobin in ß-type hemoglobinopathies patients. Within this context we aimed to investigate the extent of the LRF/ZBTB7A conservation among primates and mouse genome, focusing our interest also on the CpG island flanking the gene's promoter region, in an effort to further establish its epigenetic regulatory role in human hematopoiesis and pharmacological involvement in hematopoietic disorders. Comparative analysis of the human ZBTB7A nucleotide and amino acid sequences and orthologous sequences among non-human primates and mouse, exhibited high conservation scores. Pathway analysis, clearly indicated that LRF/ZBTB7A influences conserved cellular processes. These data in conjunction with the high levels of expression foremost in hematopoietic tissues, highlighted LRF/ZBTB7A as an essential factor operating indisputably during hematopoiesis.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Doenças Hematológicas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Sequência Conservada/genética , Ilhas de CpG/genética , Bases de Dados Genéticas , Hemoglobina Fetal/genética , Hematopoese/genética , Humanos , Camundongos , Primatas/genética , Regiões Promotoras Genéticas/genética
2.
Nat Commun ; 11(1): 3695, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728065

RESUMO

Pseudogenes are ideal markers of genome remodelling. In turn, the mouse is an ideal platform for studying them, particularly with the recent availability of strain-sequencing and transcriptional data. Here, combining both manual curation and automatic pipelines, we present a genome-wide annotation of the pseudogenes in the mouse reference genome and 18 inbred mouse strains (available via the mouse.pseudogene.org resource). We also annotate 165 unitary pseudogenes in mouse, and 303, in human. The overall pseudogene repertoire in mouse is similar to that in human in terms of size, biotype distribution, and family composition (e.g. with GAPDH and ribosomal proteins being the largest families). Notable differences arise in the pseudogene age distribution, with multiple retro-transpositional bursts in mouse evolutionary history and only one in human. Furthermore, in each strain about a fifth of all pseudogenes are unique, reflecting strain-specific evolution. Finally, we find that ~15% of the mouse pseudogenes are transcribed, and that highly transcribed parent genes tend to give rise to many processed pseudogenes.


Assuntos
Pseudogenes/genética , Transcrição Genética , Animais , Sequência Conservada/genética , Evolução Molecular , Ontologia Genética , Genoma , Humanos , Camundongos Endogâmicos C57BL , Anotação de Sequência Molecular , Especificidade da Espécie
3.
BMC Evol Biol ; 20(1): 91, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727363

RESUMO

BACKGROUND: The SIAMESE (SIM) locus is a cell-cycle kinase inhibitor (CKI) gene that has to date been identified only in plants; it encodes a protein that promotes transformation from mitosis to endoreplication. Members of the SIAMESE-RELATED (SMR) family have similar functions, and some are related to cell-cycle responses and abiotic stresses. However, the functions of SMRs are poorly understood in maize (Zea mays L.). RESULTS: In the present study, 12 putative SMRs were identified throughout the entire genome of maize, and these were clustered into six groups together with the SMRs from seven other plant species. Members of the ZmSMR family were divided into four groups according to their protein sequences. Various cis-acting elements in the upstream sequences of ZmSMRs responded to abiotic stresses. Expression analyses revealed that all ZmSMRs were upregulated at 5, 20, 25, and 35 days after pollination. In addition, we found that ZmSMR9/11/12 may have regulated the initiation of endoreplication in endosperm central cells. Additionally, ZmSMR2/10 may have been primarily responsible for the endoreplication regulation of outer endosperm or aleurone cells. The relatively high expression levels of almost all ZmSMRs in the ears and tassels also implied that these genes may function in seed development. The effects of treatments with ABA, heat, cold, salt, and drought on maize seedlings and expression of ZmSMR genes suggested that ZmSMRs were strongly associated with response to abiotic stresses. CONCLUSION: The present study is the first to conduct a genome-wide analysis of members of the ZmSMR family by investigating their locations in chromosomes, identifying regulatory elements in their promoter regions, and examining motifs in their protein sequences. Expression analysis of different endosperm developmental periods, tissues, abiotic stresses, and hormonal treatments suggests that ZmSMR genes may function in endoreplication and regulate the development of reproductive organs. These results may provide valuable information for future studies of the functions of the SMR family in maize.


Assuntos
Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Família Multigênica , Zea mays/genética , Sequência de Aminoácidos , Sequência de Bases , Cromossomos de Plantas/genética , Sequência Conservada/genética , Endosperma/genética , Duplicação Gênica , Genes de Plantas , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Análise de Regressão , Especificidade da Espécie , Estresse Fisiológico/efeitos dos fármacos , Sintenia/genética
4.
BMC Evol Biol ; 20(1): 85, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664916

RESUMO

BACKGROUND: ATP-binding cassette (ABC) transporters are involved in the active transportation of various endogenous or exogenous substances. Two ABCG2 gene subfamily members have been identified in birds. A detailed comparative study of the ABCG2 and ABCG2-like genes aid our understanding of their evolutionary history at the molecular level and provide a theoretical reference for studying the specific functions of ABCG2 and ABCG2-like genes in birds. RESULTS: We first identified 77 ABCG2/ABCG2-like gene sequences in the genomes of 41 birds. Further analysis showed that both the nucleic acid and amino acid sequences of ABCG2 and ABCG2-like genes were highly conserved and exhibited high homology in birds. However, significant differences in the N-terminal structure were found between the ABCG2 and ABCG2-like amino acid sequences. A selective pressure analysis showed that the ABCG2 and ABCG2-like genes were affected by purifying selection during the process of bird evolution. CONCLUSIONS: We believe that multiple members of the ABCG2 gene subfamily exist on chromosome 4 in the ancestors of birds. Over the long course of evolution, only the ABCG2 gene was retained on chromosome 4 in birds. The ABCG2-like gene on chromosome 6 might have originated from chromosome replication or fusion. The structural differences between the N terminus of ABCG2 protein and those of ABCG2-like proteins might lead to functional differences between the corresponding genes.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Aves/genética , Evolução Molecular , Homologia de Sequência de Aminoácidos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/química , Sequência de Aminoácidos , Animais , Cromossomos/genética , Sequência Conservada/genética , Éxons/genética , Regulação da Expressão Gênica , Genoma , Íntrons/genética , Família Multigênica , Fases de Leitura Aberta/genética , Fosforilação , Filogenia , Domínios Proteicos , Sítios de Splice de RNA/genética , Seleção Genética , Sintenia/genética
5.
Nat Commun ; 11(1): 2789, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493961

RESUMO

RNA-binding proteins play key roles in regulation of gene expression via recognition of structural features in RNA molecules. Here we apply a quantitative RNA pull-down approach to 186 evolutionary conserved RNA structures and report 162 interacting proteins. Unlike global RNA interactome capture, we associate individual RNA structures within messenger RNA with their interacting proteins. Of our binders 69% are known RNA-binding proteins, whereas some are previously unrelated to RNA binding and do not harbor canonical RNA-binding domains. While current knowledge about RNA-binding proteins relates to their functions at 5' or 3'-UTRs, we report a significant number of them binding to RNA folds in the coding regions of mRNAs. Using an in vivo reporter screen and pulsed SILAC, we characterize a subset of mRNA-RBP pairs and thus connect structural RNA features to functionality. Ultimately, we here present a generic, scalable approach to interrogate the increasing number of RNA structural motifs.


Assuntos
Sequência Conservada , Evolução Molecular , Conformação de Ácido Nucleico , RNA Fúngico/química , Saccharomyces cerevisiae/genética , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas/genética , Sequência de Bases , Sequência Conservada/genética , Epistasia Genética , Genes Reporter , Genoma Fúngico , Proteínas de Fluorescência Verde/metabolismo , Motivos de Nucleotídeos/genética , Biossíntese de Proteínas , Proteoma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Reprodutibilidade dos Testes , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
6.
PLoS One ; 15(5): e0232260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401752

RESUMO

Identical codon pairing and co-tRNA codon pairing increase translational efficiency within genes when two codons that encode the same amino acid are translated by the same tRNA before it diffuses from the ribosome. We examine the phylogenetic signal in both identical and co-tRNA codon pairing across 23 428 species using alignment-free and parsimony methods. We determined that conserved codon pairing typically has a smaller window size than the length of a ribosome, and codon pairing tracks phylogenies across various taxonomic groups. We report a comprehensive analysis of codon pairing, including the extent to which each codon pairs. Our parsimony method generally recovers phylogenies that are more congruent with the established phylogenies than our alignment-free method. However, four of the ten taxonomic groups did not have sufficient orthologous codon pairings and were therefore analyzed using only the alignment-free methods. Since the recovered phylogenies using only codon pairing largely match phylogenies from the Open Tree of Life and the NCBI taxonomy, and are comparable to trees recovered by other algorithms, we propose that codon pairing biases are phylogenetically conserved and should be considered in conjunction with other phylogenomic techniques.


Assuntos
Códon/genética , Sequência Conservada/genética , Filogenia , RNA de Transferência/genética , Ribossomos/genética
7.
RNA ; 26(9): 1234-1246, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32457084

RESUMO

The wide prevalence and regulated expression of long noncoding RNAs (lncRNAs) highlight their functional roles, but the molecular basis for their activities and structure-function relationships remains to be investigated, with few exceptions. Among the relatively few lncRNAs conserved over significant evolutionary distances is the long intergenic noncoding RNA (lincRNA) Cyrano (orthologous to human OIP5-AS1), which contains a region of 300 highly conserved nucleotides within tetrapods, which in turn contains a functional stretch of 26 nt of deep conservation. This region binds to and facilitates the degradation of the microRNA miR-7, a short ncRNA with multiple cellular functions, including modulation of oncogenic expression. We probed the secondary structure of Cyrano in vitro and in cells using chemical and enzymatic probing, and validated the results using comparative sequence analysis. At the center of the functional core of Cyrano is a cloverleaf structure maintained over the >400 million years of divergent evolution that separates fish and primates. This strikingly conserved motif provides interaction sites for several RNA-binding proteins and masks a conserved recognition site for miR-7. Conservation in this region strongly suggests that the function of Cyrano depends on the formation of this RNA structure, which could modulate the rate and efficiency of degradation of miR-7.


Assuntos
Sequência Conservada/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Animais , Humanos , Camundongos , MicroRNAs/genética , Primatas/genética , RNA Mensageiro/genética , RNA não Traduzido/genética , Peixe-Zebra
8.
Gene ; 747: 144674, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32304781

RESUMO

Very long chain fatty acids (VLCFAs) that are structural components of cell membrane lipid, cuticular waxes and seed oil, play crucial roles in plant growth, development and stress response. Fatty acid elongases (FAEs) comprising KCS and ELO, are key enzymes for VLCFA biosynthesis in plants. Although reference genomes of Brassica napus and its parental speices both have been sequenced, whole-genome analysis of FAE gene family in these Brassica speices is not reported. Here, 58, 33 and 30 KCS genes were identified in B. napus, B. rapa and B. oleracea genomes, respectively, whereas 14, 6 and 8 members were obtained for ELO genes. These KCS genes were unevenly located in 37 chromosomes and 3 scaffolds of 3 Brassica species, while these ELO genes were mapped to 19 chromosomes. The KCS and ELO proteins were divided into 8 and 4 subclasses, respectively. Gene structure and protein motifs remained highly conserved in each KCS or ELO subclass. Most promoters of KCS and ELO genes harbored various plant growth-, phytohormone-, and stress response-related cis-acting elements. 20 SSR loci existed in the KCS and ELO genes/promoters. The whole-genome duplication and segmental duplication mainly contributed to expansion of KCS and ELO genes in these genomes. Transcriptome analysis showed that KCS and ELO genes in 3 Brassica species were expressed in various tissues/organs with different levels, whereas 1 BnELO gene and 6 BnKCS genes might be pathogen-responsive genes. The qRT-PCR assay showed that BnKCS22 and BnELO04 responded to various phytohormone treatments and abiotic stresses. This work lays the foundation for further function identification of KCS and ELO genes in B. napus and its progenitors.


Assuntos
Brassica napus/enzimologia , Brassica napus/genética , Elongases de Ácidos Graxos/genética , Genes de Plantas , Estudo de Associação Genômica Ampla , Família Multigênica , Brassica napus/efeitos dos fármacos , Cromossomos de Plantas/genética , Sequência Conservada/genética , Duplicação Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Loci Gênicos , Repetições de Microssatélites/genética , Motivos de Nucleotídeos , Filogenia , Reguladores de Crescimento de Planta/farmacologia , Sequências Reguladoras de Ácido Nucleico/genética , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Sintenia/genética
9.
PLoS One ; 15(4): e0231020, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294100

RESUMO

The mitochondrial genomes of flowering plants are well known for their large size, variable coding-gene set and fluid genome structure. The available mitochondrial genomes of the early angiosperms show extreme genetic diversity in genome size, structure, and sequences, such as rampant HGTs in Amborella mt genome, numerous repeated sequences in Nymphaea mt genome, and conserved gene evolution in Liriodendron mt genome. However, currently available early angiosperm mt genomes are still limited, hampering us from obtaining an overall picture of the mitogenomic evolution in angiosperms. Here we sequenced and assembled the draft mitochondrial genome of Magnolia biondii Pamp. from Magnoliaceae (magnoliids) using Oxford Nanopore sequencing technology. We recovered a single linear mitochondrial contig of 967,100 bp with an average read coverage of 122 × and a GC content of 46.6%. This draft mitochondrial genome contains a rich 64-gene set, similar to those of Liriodendron and Nymphaea, including 41 protein-coding genes, 20 tRNAs, and 3 rRNAs. Twenty cis-spliced and five trans-spliced introns break ten protein-coding genes in the Magnolia mt genome. Repeated sequences account for 27% of the draft genome, with 17 out of the 1,145 repeats showing recombination evidence. Although partially assembled, the approximately 1-Mb mt genome of Magnolia is still among the largest in angiosperms, which is possibly due to the expansion of repeated sequences, retention of ancestral mtDNAs, and the incorporation of nuclear genome sequences. Mitochondrial phylogenomic analysis of the concatenated datasets of 38 conserved protein-coding genes from 91 representatives of angiosperm species supports the sister relationship of magnoliids with monocots and eudicots, which is congruent with plastid evidence.


Assuntos
Genoma Mitocondrial/genética , Genoma de Planta/genética , Magnolia/genética , Magnoliopsida/genética , Mitocôndrias/genética , Sequência Conservada/genética , Genes de Plantas/genética , Liriodendron/genética , Anotação de Sequência Molecular , Nymphaea/genética , Filogenia
10.
RNA ; 26(7): 784-793, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32241834

RESUMO

Long noncoding RNAs (lncRNAs) have recently emerged as prominent regulators of gene expression in eukaryotes. LncRNAs often drive the modification and maintenance of gene activation or gene silencing states via chromatin conformation rearrangements. In plants, lncRNAs have been shown to participate in gene regulation, and are essential to processes such as vernalization and photomorphogenesis. Despite their prominent functions, only over a dozen lncRNAs have been experimentally and functionally characterized. Similar to its animal counterparts, the rates of sequence divergence are much higher in plant lncRNAs than in protein coding mRNAs, making it difficult to identify lncRNA conservation using traditional sequence comparison methods. Beyond this, little is known about the evolutionary patterns of lncRNAs in plants. Here, we characterized the splicing conservation of lncRNAs in Brassicaceae. We generated a whole-genome alignment of 16 Brassica species and used it to identify synthenic lncRNA orthologs. Using a scoring system trained on transcriptomes from A. thaliana and B. oleracea, we identified splice sites across the whole alignment and measured their conservation. Our analysis revealed that 17.9% (112/627) of all intergenic lncRNAs display splicing conservation in at least one exon, an estimate that is substantially higher than previous estimates of lncRNA conservation in this group. Our findings agree with similar studies in vertebrates, demonstrating that splicing conservation can be evidence of stabilizing selection. We provide conclusive evidence for the existence of evolutionary deeply conserved lncRNAs in plants and describe a generally applicable computational workflow to identify functional lncRNAs in plants.


Assuntos
Sequência Conservada/genética , Processamento de RNA/genética , RNA Longo não Codificante/genética , RNA de Plantas/genética , Arabidopsis/genética , Brassica/genética , Evolução Molecular , Genoma de Planta/genética , RNA Mensageiro/genética
11.
PLoS One ; 15(3): e0230236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214344

RESUMO

Pathways leading to formation of non-coding RNA and protein genes are varied and complex. We report finding a conserved repeat sequence present in human and chimpanzee genomes that appears to have originated from a common primate ancestor. This sequence is repeatedly copied in human chromosome 22 (chr22) low copy repeats (LCR22) or segmental duplications and forms twenty-one different genes, which include the human long intergenic non-coding RNA (lincRNA) family FAM230, a newly discovered lincRNA gene family termed conserved long intergenic non-coding RNAs (clincRNA), pseudogene families, as well as the gamma-glutamyltransferase (GGT) protein gene family and the RNA pseudogenes that originate from GGT sequences. Of particular interest are the GGT5 and USP18 protein genes that appear to have formed from an homologous repeat sequence that also forms the clincRNA gene family. The data point to ancestral DNA sequences, conserved through evolution and duplicated in humans by chromosomal repeat sequences that may serve as functional genomic elements in the development of diverse genes.


Assuntos
Proteínas/genética , Pseudogenes/genética , RNA Longo não Codificante/genética , Animais , Proteínas de Transporte/genética , Mapeamento Cromossômico/métodos , Sequência Conservada/genética , Elementos de DNA Transponíveis/genética , Evolução Molecular , Humanos , Pan troglodytes/genética , gama-Glutamiltransferase/genética
12.
Mol Phylogenet Evol ; 147: 106777, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32126279

RESUMO

Evolution of Brassica genome post-polyploidization reveals asymmetrical genome fractionation and copy number variation. Herein, we describe the impact of promoter divergence among SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) homeologs on expression and function in Brassica spp. SOC1, a regulated floral pathway integrator, is conserved as 3 redundant homeologs in diploid Brassicas. Even with high sequence identity within coding regions (92.8-100%), the spatio-temporal expression patterns of 9 SOC1 homologs in B. juncea and B. nigra indicates regulatory divergence. While LF and MF2 SOC1 homeologs are upregulated during floral transition, MF1 is barely expressed. Also, MF2 homeolog levels do not decline post-flowering, unlike LF. To investigate the underlying source of divergence, we analyzed the sequence and phylogeny of all reported (22) and isolated (21) upstream regions of Brassica SOC1. Full length upstream regions (4712-19189 bp) reveal 5 ubiquitously conserved ancestral Blocks, harboring binding sites of 18 TFs (TFBSs) characterized in Arabidopsis thaliana. The orthologs of these TFBSs are differentially conserved among Brassica SOC1 homeologs, imparting expression divergence. No crucial TFBSs are exclusively lost from LF_SOC1 promoter, while MF1_SOC1 has lost NF-Y binding site crucial for SOC1 activation by CONSTANS. MF2_SOC1 homeologs have lost important TFBSs (SEP3, AP1 and SMZ), responsible for SOC1 repression post-flowering. BjuAALF_SOC1 promoter (proximal 2 kb) shows ubiquitous reporter expression in B. juncea cv. Varuna transgenics, while BjuAAMF1_SOC1 promoter shows absence of reporter expression, validating the impact of TFBS divergence. Conservation of the original primary protein sequence is discovered in B. rapa homeologs (46) of 18 TFs. Co-regulation pattern of these TFs appeared similar for B. rapa LF and MF2 SOC1 homeologs; MF1 shows significant variation. Strong regulatory association is recorded for AP1, AP2, SEP3, FLC and CONSTANS/NF-Y, highlighting their importance in homeolog-specific SOC1 regulation. Correlation of B. juncea AP1, AP2 and FLC expression with SOC1 homeologs also complies with the TFBS differences. We thus conclude that redundant SOC1 loci contribute differentially to cumulative expression of SOC1 due to divergent selection of ancestral TFBSs.


Assuntos
Brassica/genética , Sequência Conservada , Evolução Molecular , Flores/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Homologia de Sequência do Ácido Nucleico , Fatores de Transcrição/metabolismo , Sequência de Bases , Sítios de Ligação , Brassica/metabolismo , Sequência Conservada/genética , Variações do Número de Cópias de DNA/genética , Genes Reporter , Filogenia , Poliploidia , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo
13.
Nucleic Acids Res ; 48(6): 3103-3118, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32025695

RESUMO

Micro (mi)RNAs are 20-22nt long non-coding RNA molecules involved in post-transcriptional silencing of targets having high base-pair complementarity. Plant miRNAs are processed from long Pol II-transcripts with specific stem-loop structures by Dicer-like (DCL) 1 protein. Although there were reports indicating how a specific region is selected for miRNA biogenesis, molecular details were unclear. Here, we show that the presence of specific GC-rich sequence signature within miRNA/miRNA* region is required for the precise miRNA biogenesis. The involvement of GC-rich signatures in precise processing and abundance of miRNAs was confirmed through detailed molecular and functional analysis. Consistent with the presence of the miRNA-specific GC signature, target RNAs of miRNAs also possess conserved complementary sequence signatures in their miRNA binding motifs. The selection of these GC signatures was dependent on an RNA binding protein partner of DCL1 named HYL1. Finally, we demonstrate a direct application of this discovery for enhancing the abundance and efficiency of artificial miRNAs that are popular in plant functional genomic studies.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Proteínas de Ciclo Celular/genética , MicroRNAs/biossíntese , Proteínas de Ligação a RNA/genética , Ribonuclease III/genética , Sequência Conservada/genética , Sequência Rica em GC/genética , Regulação da Expressão Gênica de Plantas/genética , MicroRNAs/genética , RNA de Plantas/genética , Motivos de Ligação ao RNA/genética
14.
BMC Evol Biol ; 20(1): 33, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32106815

RESUMO

BACKGROUND: Human chromosome 19 has many unique characteristics including gene density more than double the genome-wide average and 20 large tandemly clustered gene families. It also has the highest GC content of any chromosome, especially outside gene clusters. The high GC content and concomitant high content of hypermutable CpG sites raises the possibility chromosome 19 exhibits higher levels of nucleotide diversity both within and between species, and may possess greater variation in DNA methylation that regulates gene expression. RESULTS: We examined GC and CpG content of chromosome 19 orthologs across representatives of the primate order. In all 12 primate species with suitable genome assemblies, chromosome 19 orthologs have the highest GC content of any chromosome. CpG dinucleotides and CpG islands are also more prevalent in chromosome 19 orthologs than other chromosomes. GC and CpG content are generally higher outside the gene clusters. Intra-species variation based on SNPs in human common dbSNP, rhesus, crab eating macaque, baboon and marmoset datasets is most prevalent on chromosome 19 and its orthologs. Inter-species comparisons based on phyloP conservation show accelerated nucleotide evolution for chromosome 19 promoter flanking and enhancer regions. These same regulatory regions show the highest CpG density of any chromosome suggesting they possess considerable methylome regulatory potential. CONCLUSIONS: The pattern of high GC and CpG content in chromosome 19 orthologs, particularly outside gene clusters, is present from human to mouse lemur representing 74 million years of primate evolution. Much CpG variation exists both within and between primate species with a portion of this variation occurring in regulatory regions.


Assuntos
Cromossomos Humanos Par 19/genética , Sequência Conservada , Primatas/classificação , Primatas/genética , Animais , Composição de Bases , Sequência de Bases , Cromossomos/genética , Sequência Conservada/genética , Ilhas de CpG , Metilação de DNA , Fosfatos de Dinucleosídeos/genética , Genoma , Humanos , Lemur/classificação , Lemur/genética , Camundongos , Família Multigênica , Filogenia , Regiões Promotoras Genéticas/genética , Sequências Reguladoras de Ácido Nucleico/genética
15.
BMC Genomics ; 21(1): 8, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896347

RESUMO

BACKGROUND: Pineapple is the most important crop with CAM photosynthesis, but its molecular biology is underexplored. MADS-box genes are crucial transcription factors involving in plant development and several biological processes. However, there is no systematic analysis of MADS-box family genes in pineapple (Ananas comosus). RESULTS: Forty-eight MADS-box genes were identified in the pineapple genome. Based on the phylogenetic studies, pineapple MADS-box genes can be divided into type I and type II MADS-box genes. Thirty-four pineapple genes were classified as type II MADS-box genes including 32 MIKC-type and 2 Mδ-type, while 14 type I MADS-box genes were further divided into Mα, Mß and Mγ subgroups. A majority of pineapple MADS-box genes were randomly distributed across 19 chromosomes. RNA-seq expression patterns of MADS-box genes in four different tissues revealed that more genes were highly expressed in flowers, which was confirmed by our quantitative RT-PCR results. There is no FLC and CO orthologs in pineapple. The loss of FLC and CO orthologs in pineapple indicated that modified flowering genes network in this tropical plant compared with Arabidopsis. The expression patterns of MADS-box genes in photosynthetic and non-photosynthetic leaf tissues indicated the potential roles of some MADS-box genes in pineapple CAM photosynthesis. The 23% of pineapple MADS-box genes showed diurnal rhythm, indicating that these MADS-box genes are regulated by circadian clock. CONCLUSIONS: MADS-box genes identified in pineapple are closely related to flowering development. Some MADS-box genes are involved in CAM photosynthesis and regulated by the circadian clock. These findings will facilitate research on the development of unusual spiral inflorescences on pineapple fruit and CAM photosynthesis.


Assuntos
Ananas/genética , Flores/genética , Proteínas de Domínio MADS/genética , Fotossíntese/genética , Ananas/crescimento & desenvolvimento , Arabidopsis/genética , Sequência Conservada/genética , Evolução Molecular , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/genética , Redes Reguladoras de Genes/genética , Genoma de Planta/genética , Família Multigênica/genética , Filogenia , Desenvolvimento Vegetal/genética
16.
Nucleic Acids Res ; 48(5): 2661-2675, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-31915815

RESUMO

The occurrence of group II introns in plant mitochondrial genomes is strikingly different between the six major land plant clades, contrasting their highly conserved counterparts in chloroplast DNA. Their present distribution likely reflects numerous ancient intron gains and losses during early plant evolution before the emergence of seed plants. As a novelty for plant organelles, we here report on five cases of twintrons, introns-within-introns, in the mitogenomes of lycophytes and hornworts. An internal group II intron interrupts an intron-borne maturase of an atp9 intron in Lycopodiaceae, whose splicing precedes splicing of the external intron. An invasive, hypermobile group II intron in cox1, has conquered nine further locations including a previously overlooked sdh3 intron and, most surprisingly, also itself. In those cases, splicing of the external introns does not depend on splicing of the internal introns. Similar cases are identified in the mtDNAs of hornworts. Although disrupting a group I intron-encoded protein in one case, we could not detect splicing of the internal group II intron in this 'mixed' group I/II twintron. We suggest the name 'zombie' twintrons (half-dead, half-alive) for such cases where splicing of external introns does not depend any more on prior splicing of fossilized internal introns.


Assuntos
Íntrons/genética , Lycopodiaceae/genética , Mitocôndrias/genética , Sequência de Bases , Sequência Conservada/genética , Evolução Molecular , Hepatófitas/genética , Conformação de Ácido Nucleico , Filogenia , Terminologia como Assunto
17.
Nucleic Acids Res ; 48(6): 2924-2941, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-31996893

RESUMO

WDR5 is a highly-conserved nuclear protein that performs multiple scaffolding functions in the context of chromatin. WDR5 is also a promising target for pharmacological inhibition in cancer, with small molecule inhibitors of an arginine-binding pocket of WDR5 (the 'WIN' site) showing efficacy against a range of cancer cell lines in vitro. Efforts to understand WDR5, or establish the mechanism of action of WIN site inhibitors, however, are stymied by its many functions in the nucleus, and a lack of knowledge of the conserved gene networks-if any-that are under its control. Here, we have performed comparative genomic analyses to identify the conserved sites of WDR5 binding to chromatin, and the conserved genes regulated by WDR5, across a diverse panel of cancer cell lines. We show that a specific cohort of protein synthesis genes (PSGs) are invariantly bound by WDR5, demonstrate that the WIN site anchors WDR5 to chromatin at these sites, and establish that PSGs are bona fide, acute, and persistent targets of WIN site blockade. Together, these data reveal that WDR5 plays a predominant transcriptional role in biomass accumulation and provide further evidence that WIN site inhibitors act to repress gene networks linked to protein synthesis homeostasis.


Assuntos
Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Biossíntese de Proteínas/genética , Sequência de Bases , Sítios de Ligação/genética , Linhagem Celular , Cromatina/metabolismo , Sequência Conservada/genética , Feminino , Humanos , Masculino , Ligação Proteica , Transcrição Genética , Proteína Supressora de Tumor p53/metabolismo
18.
J Biosci ; 452020.
Artigo em Inglês | MEDLINE | ID: mdl-31965988

RESUMO

S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases (MTases) are involved in diverse cellular functions. These enzymes show little sequence conservation but have a conserved structural fold. The DNA MTases have characteristic motifs that are involved in AdoMet binding, DNA target recognition and catalysis. Motif III of these MTases have a highly conserved acidic residue, often an aspartate, whose functional significance is not clear. Here, we report a mutational study of the residue in the ß family MTase of the Type III restriction-modification enzyme EcoP15I. Replacement of this residue by alanine affects its methylation activity. We propose that this residue contributes to the affinity of the enzyme for AdoMet. Analysis of the structures of DNA, RNA and protein MTases reveal that the acidic residue is conserved in all of them, and interacts with N6 of the adenine moiety of AdoMet. Interestingly, in the SET-domain protein lysine MTases, which have a fold different from other AdoMet-dependent MTases, N6 of the adenine moiety is hydrogen bonded to the main chain carbonyl group of the histidine residue of the highly conserved motif III. Our study reveals the evolutionary conservation of a carbonyl group in DNA, RNA and protein AdoMet-dependent MTases for specific interaction by hydrogen bond with AdoMet, despite the lack of overall sequence conservation.


Assuntos
DNA/genética , Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/ultraestrutura , Proteínas Repressoras/ultraestrutura , DNA Metiltransferases Sítio Específica (Adenina-Específica)/ultraestrutura , Sequência de Aminoácidos/genética , Sequência Conservada/genética , DNA/ultraestrutura , Metilação de DNA/genética , Enzimas de Restrição-Modificação do DNA/genética , Enzimas de Restrição-Modificação do DNA/ultraestrutura , Humanos , Ligação de Hidrogênio , Metiltransferases/ultraestrutura , Mutagênese Sítio-Dirigida , Conformação de Ácido Nucleico , Conformação Proteica , Conformação Proteica em Folha beta/genética , Dobramento de Proteína , Proteína-Arginina N-Metiltransferases/genética , RNA/genética , RNA/ultraestrutura , Proteínas Repressoras/genética , S-Adenosilmetionina/metabolismo , DNA Metiltransferases Sítio Específica (Adenina-Específica)/genética
19.
J Biosci ; 452020.
Artigo em Inglês | MEDLINE | ID: mdl-31965990

RESUMO

The epigenetic memory is an essential aspect of multicellular organisms to maintain several cell types and their gene expression pattern. This complex process uses a number of protein factors and specific DNA elements within the developmental cues to achieve this. The protein factors involved in the process are the Polycomb group (PcG) members, and, accordingly, the DNA sequences that interact with these proteins are called Polycomb Response Elements (PREs). Since the PcG proteins are highly conserved among higher eukaryotes, including insects, and function at thousands of sites in the genomes, it is expected that PREs mayalso be present across the genome.However, the studies on PREs in insect species, other thanDrosophila, is currently lacking.We took a bioinformatics approach to develop an inclusive PRE prediction tool, 'PRE Mapper', to address this need. By applying this tool on the Drosophila melanogaster genome, we predicted greater than 20,000 PREs.When comparedwith the available PRE prediction methods, this tool shows far better performance by correctly identifying the in vivo binding sites of PcG proteins, identified by genome-scale ChIP experiments. Further analysis of the predicted PREs shows their cohabitation with chromatin domain boundary elements at several places in the Drosophila genome, possibly defining a composite epigenetic module.We analysed 10 insect genomes in this context and find several conserved features in PREs across the insect species with some variations in their occurrence frequency. These analyses leading to the identification of PREin insect genomes contribute to our understanding of epigenetic mechanisms in these organisms.


Assuntos
Proteínas de Ligação a DNA/genética , Genômica , Proteínas do Grupo Polycomb/genética , Ligação Proteica/genética , Animais , Sítios de Ligação/genética , Cromatina/genética , Sequência Conservada/genética , DNA/genética , Epigênese Genética/genética , Regulação da Expressão Gênica no Desenvolvimento , Genoma de Inseto/genética , Insetos/genética , Elementos de Resposta/genética
20.
Gene ; 727: 144231, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31707000

RESUMO

Autophagy is the cellular process of removal of misfolded or damaged macromolecules and organelles. Experimental studies have demonstrated autophagy as a major mechanism of lifespan extension in long-lived mammals such as bats and mole rat rodents. Moreover, the role of this biological process has been well documented in protection against age-associated diseases and viral infection. However, studies on the molecular adaptive changes of autophagy factors during evolution are scarce. Here, we conducted a bioinformatics study of the molecular evolution of the Lysosomal Associated Membrane Protein 2 (LAMP2), as a rate-limiting factor in the lysosomal degradation stage of autophagy (the communal step of two of autophagy types: macroautophagy and chaperone-mediated). Analyzing LAMP2 across placental mammals, our phylogenetic-based maximum likelihood analyses indicate that the majority of the coding sites undergo purifying selection. However, around 27% of sites display a relaxation of purifying constraints (average ω = 0.42128), among which, 14 particular sites undergo positive selection (ω > 1). These sites are mostly located in the first luminal domain of LAMP2 (N-domain), with a hotspot region in the 135-144 codons interval. Therefore, the N-domain may account for the functional diversity and regulation of LAMP2. In addition, the identified positive selection sites could act as key regulatory sites in the LAMP2 function. On the other hand, testing the rate of evolution in LAMP2 along different clades of placental mammals revealed a relatively relaxed evolution in LAMP2 along megabats' clade. It is not clear yet whether an expedited evolution of LAMP2 in megabats has contributed to their reported up-regulation of autophagy. Finally, our data indicate positive selection sites along the ancestral branch of the clades of rodents, mouse-related rodents, and mole-rats; and suggest the potentially important regulatory role of these sites in LAMP2. Identifying the residues under positive selection, our findings pave the way for future experimental investigations to define how these selective substitutions have functionally affected autophagy.


Assuntos
Eutérios/genética , Proteína 2 de Membrana Associada ao Lisossomo/genética , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Adaptação Biológica/genética , Animais , Autofagia/genética , Sequência Conservada/genética , Eutérios/metabolismo , Evolução Molecular , Humanos , Mamíferos/genética , Mamíferos/metabolismo , Taxa de Mutação , Filogenia , Análise de Sequência de DNA/métodos
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