检索结果-内蒙古大学图书馆

A meta-analysis of the genomic and transcriptomic composition of complex life

CELL CYCLE 2013年第13期12卷 2061-2072页

作者： Liu, Ganqiang Mattick, John S. Taft, Ryan J. Univ Queensland Inst Mol Biosci Brisbane Qld Australia St Vincents Hosp Garvan Inst Med Res Darlinghurst NSW 2010 Australia

It is now clear that animal genomes are predominantly non-protein-coding, and that these sequences encode a wide array of RNA transcripts and other regulatory elements that are fundamental to the development of complex life. We have previously argued that the proportion of an animal genome that is non-protein-coding dna (ncdna) correlates well with its apparent biological complexity. Here we extend on that work and, using data from a total of 1,627 prokaryotic and 153 eukaryotic complete and annotated genomes, show that the proportion of ncdna per haploid genome is significantly positively correlated with a previously published proxy of biological complexity, the number of distinct cell types. This is in contrast to the amount of the genome that encodes proteins, which we show is essentially unchanged across Metazoa. Furthermore, using a total of 179 RNA-seq data sets from nematode (47), fruit fly (72), zebrafish (20) and human (42), we show, consistent with other recent reports, that the vast majority of ncdna in animals is transcribed. This includes more than 60 human loci previously considered "gene deserts," many of which are expressed tissue-specifically and associated with previously reported GWAS SNPs. These results suggest that ncdna, and the ncRNAs encoded within it, may be intimately involved in the evolution, maintenance and development of complex life.

关键词： noncoding RNA non-coding dna evolution complexity lincRNA small RNA

来源：评论

学校读者我要写书评

暂无评论

Patterns of variation in cis-regulatory regions: examining evidence of purifying selection

引用

BMC GENOMICS 2018年第1期19卷 1-14页

作者： Naidoo, Thijessen Sjodin, Per Schlebusch, Carina Jakobsson, Mattias Uppsala Univ Dept Organismal Biol Uppsala Sweden Sci Life Lab Uppsala Sweden

Background: With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements. Results: We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations. Conclusions: In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements.

关键词： Regulatory regions Purifying selection Selection efficacy non-coding dna Functional elements Population genetics

来源：评论

学校读者我要写书评

暂无评论

Evolutionary Constraint in Flanking Regions of Avian Genes

引用

MOLECULAR BIOLOGY AND EVOLUTION 2011年第9期28卷 2481-2489页

作者： Kunstner, Axel Nabholz, Benoit Ellegren, Hans Uppsala Univ Dept Evolutionary Biol Evolutionary Biol Ctr Uppsala Sweden

An important comprehension from comparative genomic analysis is that sequence conservation beyond neutral expectations is frequently found outside protein-coding regions, indicating important functional roles of noncoding dna. Understanding the causes of constraint on noncoding sequence evolution forms an important area of research, not least in light of the importance for understanding the evolution of gene expression. We aligned all orthologous genes of chicken and zebra finch together with 5 kb of their upstream and downstream noncoding sequences, to study the evolution of gene flanking sequences in the avian genome. Using ancestral repeats as a neutral reference, we detected significant evolutionary constraint in the 3' flanking region, highest directly after termination (60%) and then gradually decreasing to about 20% 5 kb downstream. Constraint was higher in annotated 3' untranslated regions (UTRs) than in non-UTRs at the same distance from the stop codon and higher in sequences annotated as microRNA (miRNA)-binding sites than in non-miRNA-binding sites within 3' UTRs. Constraint was also higher when estimated for a smaller data set of genes from more closely related songbird species, indicating turnover of functional elements during avian evolution. On the 5' flanking side constraint was readily seen within the first 125 bp immediately upstream of the start codon (34%) and was about 10% for remaining sequence within 5 kb upstream. Analysis of chicken polymorphism data gave further support for the highest constraint directly before and after the translated region. Finally, we found that genes evolving under the highest constraint measured by d(N)/d(S) also had the highest level of constraint in the 3' flanking region. This study broadens the insights into gene flanking sequence evolution by adding new findings from a vertebrate lineage other than mammals.

关键词： UTR non-coding dna purifying selection chicken zebra finch

来源：评论

学校读者我要写书评

暂无评论

Systematic mapping of functional enhancer-promoter connections with CRISPR interference

引用

SCIENCE 2016年第6313期354卷 769-773页

作者： Fulco, Charles P. Munschauer, Mathias Anyoha, Rockwell Munson, Glen Grossman, Sharon R. Perez, Elizabeth M. Kane, Michael Cleary, Brian Lander, Eric S. Engreitz, Jesse M. Broad Inst MIT & Harvard Cambridge MA 02142 USA Harvard Med Sch Dept Syst Biol Boston MA 02115 USA MIT Div Hlth Sci & Technol Cambridge MA 02139 USA MIT Dept Biol 77 Massachusetts Ave Cambridge MA 02139 USA MIT Computat & Syst Biol Program 77 Massachusetts Ave Cambridge MA 02139 USA

Gene expression in mammals is regulated by noncoding elements that can affect physiology and disease, yet the functions and target genes of most noncoding elements remain unknown. We present a high-throughput approach that uses clustered regularly interspaced short palindromic repeats (CRISPR) interference (CRISPRi) to discover regulatory elements and identify their target genes. We assess >1 megabase of sequence in the vicinity of two essential transcription factors, MYC and GATA1, and identify nine distal enhancers that control gene expression and cellular proliferation. Quantitative features of chromatin state and chromosome conformation distinguish the seven enhancers that regulate MYC from other elements that do not, suggesting a strategy for predicting enhancer-promoter connectivity. This CRISPRi-based approach can be applied to dissect transcriptional networks and interpret the contributions of noncoding genetic variation to human disease.

关键词： CRISPRS (Genetics) GENE expression non-coding dna TRANSCRIPTION factors CELL proliferation CHROMATIN CHROMOSOMES

来源：评论

学校读者我要写书评

暂无评论

Beyond the exome: the role of non-coding somatic mutations in cancer

引用

ANNALS OF ONCOLOGY 2016年第2期27卷 240-248页

作者： Piraino, S. W. Furney, S. J. Univ Coll Dublin Sch Med Conway Inst Biomol & Biomed Res Dublin 4 Ireland

The comprehensive identification of mutations contributing to the development of cancer is a priority of large cancer sequencing projects. To date, most studies have scrutinized mutations in coding regions of the genome, but several recent discoveries, including the identification of recurrent somatic mutations in the TERT promoter in multiple cancer types, support the idea that mutations in non-coding regions are also important in tumour development. Furthermore, analysis of whole-genome sequencing data from tumours has elucidated novel mutational patterns and processes etched into cancer genomes. Here, we present an overview of insights gleaned from the analysis of mutations from sequenced cancer genomes. We then review the mechanisms by which non-coding mutations can play a role in cancer. Finally, we discuss recent efforts aimed at identifying non-coding driver mutations, as well as the unique challenges that the analysis of non-coding mutations present in contrast to the identification of driver mutations in coding regions.

关键词： whole-genome sequencing driver mutations non-coding dna mutational signatures

来源：评论

学校读者我要写书评

暂无评论

Evidence for a slightly deleterious effect of intron polymorphisms at the EF1α gene in the deep-sea hydrothermal vent bivalve Bathymodiolus

引用

GENE 2007年第1-2期406卷 99-107页

作者： Faure, B. Bierne, N. Tanguy, A. Bonhomme, F. Jollivet, D. UPMC CNRS Biol Stn UMR 7144 F-29682 Roscoff France Univ Montpellier 2 CNRS UM2 Inst Sci EvolutUMR5554 Dept Integrat Biol F-34095 Montpellier France

A multilocus analysis was initiated in order to infer the general effect of demography and the indirect effect of positive selection on some chromosome segments in Bathymodiolus. Mussels of the genus Bathymodiolus inhabit the very hostile, fragmented and variable environment of deep-sea hydrothermal vents which is thought to cause recurrent population bottlenecks via extinction/colonisation processes and adaptation to new environmental conditions. In the course of this work we discovered that the assumption of neutrality of non-coding polymorphisms usually made in genome scan experiments was likely to be violated at one of the loci we analysed. The direct effect of slight purifying selection on non-coding polymorphisms shares many resemblances with the indirect effect of positive selection through genetic hitchhiking. Combining polymorphism with divergence data for several closely related species allowed us to obtain different expectations for the direct effect of negative selection and the indirect effect of positive selection. We observed a strong excess of rare non-coding polymorphisms at the second intron of the EF1 alpha gene in the two species Bathymodiolus azoricus and Bathymodiolus thermophilus, while two other loci, the mitochondrial COI gene and an intron of the Lysozyme gene, did not exhibit such a deviation. In addition, the divergence rate of the EF1 alpha intron was estimated to be unexpectedly low when calibrated using the closure of the Panama Isthmus that interrupted gene flow between the two species. The polymorphism to divergence ratio was similar to the one observed for the other two loci, in accordance to the hypothesis of purifying selection. We conclude that slight purifying selection is likely to act on polymorphic intronic mutations of the EF1 alpha second intron and discuss the possible relationship with the specific biology of Bathymodiolus mussels. (C) 2007 Elsevier B.V. All rights reserved.

关键词： deleterious mutations selective sweep gene genealogies non-coding dna vent species

来源：评论

学校读者我要写书评

暂无评论

motifbreakR: an R/Bioconductor package for predicting variant effects at transcription factor binding sites

引用

BIOINFORMATICS 2015年第23期31卷 3847-3849页

作者： Coetzee, Simon G. Coetzee, Gerhard A. Hazelett, Dennis J. Cedars Sinai Med Ctr Bioinformat & Computat Biol Res Ctr Los Angeles CA 90048 USA USC Norris Comprehens Canc Ctr Dept Urol & Prevent Med Los Angeles CA USA

The Summary: Functional annotation represents a key step toward the understanding and interpretation of germline and somatic variation as revealed by genome-wide association studies (GWAS) and The Cancer Genome Atlas (TCGA), respectively. GWAS have revealed numerous genetic risk variants residing in non-coding dna associated with complex diseases. For sequences that lie within enhancers or promoters of transcription, it is not straightforward to assess the effects of variants on likely transcription factor binding sites. Consequently we introduce motifbreakR, which allows the biologist to judge whether the sequence surrounding a polymorphism or mutation is a good match, and how much information is gained or lost in one allele of the polymorphism or mutation relative to the other. MotifbreakR is flexible, giving a choice of algorithms for interrogation of genomes with motifs from many public sources that users can choose from. MotifbreakR can predict effects for novel or previously described variants in public databases, making it suitable for tasks beyond the scope of its original design. Lastly, it can be used to interrogate any genome curated within bioconductor.

关键词： RESEARCH Germ cells non-coding dna Genetic polymorphisms Transcription factors Binding sites (Biochemistry)

来源：评论

学校读者我要写书评

暂无评论

引用

GENE 1999年第1期232卷 87-95页

作者： Frontali, C Pizzi, E Ist Super Sanita Cell Biol Lab I-00161 Rome Italy

A method is presented which allows detection of a sequence correlation effect not related to patchiness in base composition or to preferences in codon usage. Recurrence plots providing local views of oligonucleotide recurrence regimen show that introns and intergenic regions are often characterised by a highly recurrent use of oligonucleotides. By window analysis it is possible to score a long sequence for the recurrence of a given subset of oligos while filtering away the effects of short-range correlations. Long-range exploration of chromosome III from Caenorhabditis elegans reveals that consistent use of recurrent oligonucleotides in introns and intergenic regions generates a correlation effect that extends over several megabases. (C) 1999 Elsevier Science B.V. All rights reserved.

关键词： Caenorhabditis elegans correlation structure genome organisation non-coding dna recurrence sequence analysis

来源：评论

学校读者我要写书评

暂无评论

Evolutionary coupling between the deleteriousness of gene mutations and the amount of non-coding sequences

引用

JOURNAL OF THEORETICAL BIOLOGY 2007年第4期244卷 621-630页

作者： Knibbe, Carole Mazet, Olivier Chaudier, Fabien Fayard, Jean-Michel Beslon, Guillaume Inst Natl Sci Appl Dept Comp Sci F-69621 Villeurbanne France Inst Natl Sci Appl INRA UMR 203 Lab Biol Fonct Insectes & Interact F-69621 Villeurbanne France Inst Natl Sci Appl Camille Jordan Inst Math F-69621 Villeurbanne France Inst Natl Sci Appl Dept Biosci F-69621 Villeurbanne France

The phenotypic effects of random mutations depend on both the architecture of the genome and the gene-trait relationships. Both levels thus play a key role in the mutational variability of the phenotype, and hence in the long-term evolutionary success of the lineage. Here, by simulating the evolution of organisms with flexible genomes, we show that the need for an appropriate phenotypic variability induces a relationship between the deleteriousness of gene mutations and the quantity of non-coding sequences maintained in the genome. The more deleterious the gene mutations, the shorter the intergenic sequences. Indeed, in a shorter genome, fewer genes are affected by rearrangements (duplications, deletions, inversions, translocations) at each replication, which compensates for the higher impact of each gene mutation. This spontaneous adjustment of genome structure allows the organisms to retain the same average fitness loss per replication, despite the higher impact of single gene mutations. These results show how evolution can generate unexpected couplings between distinct organization levels. (c) 2006 Elsevier Ltd. All rights reserved.

关键词： genome evolution non-coding dna mutation effect variability robustness

来源：评论

学校读者我要写书评

暂无评论

LncRNA/dna binding analysis reveals losses and gains and lineage specificity of genomic imprinting in mammals

引用

BIOINFORMATICS 2017年第10期33卷 1431-1436页

作者： Liu, Haihua Shang, Xiaoxiao Zhu, Hao Southern Med Univ Sch Basic Med Sci Bioinformat Sect Guangzhou 510515 Guangdong Peoples R China

Motivation: Genomic imprinting is regulated by lncRNAs and is important for embryogenesis, physiology and behaviour in mammals. Aberrant imprinting causes diseases and disorders. Experimental studies have examined genomic imprinting primarily in humans and mice, thus leaving some fundamental issues poorly addressed. The cost of experimentally examining imprinted genes in many tissues in diverse species makes computational analysis of lncRNAs' dna binding sites valuable. Results: We performed lncRNA/dna binding analysis in imprinting clusters from multiple mammalian clades and discovered the following: (i) lncRNAs and imprinting sites show significant losses and gains and distinct lineage-specificity;(ii) binding of lncRNAs to promoters of imprinted genes may occur widely throughout the genome;(iii) a considerable number of imprinting sites occur in only evolutionarily more derived species;and (iv) multiple lncRNAs may bind to the same imprinting sites, and some lncRNAs have multiple dna binding motifs. These results suggest that the occurrence of abundant lncRNAs in mammalian genomes makes genomic imprinting a mechanism of adaptive evolution at the epigenome level. Supplementary information: Supplementary data are available at Bioinformatics online.

关键词： GENOMIC imprinting non-coding RNA dna-binding proteins non-coding dna EMBRYOLOGY

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：