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The Plant Journal : For Cell and... Feb 2018Pseudogenes have a reputation of being 'evolutionary relics' or 'junk DNA'. While they are well characterized in mammals, studies in more complex plant genomes have so...
Pseudogenes have a reputation of being 'evolutionary relics' or 'junk DNA'. While they are well characterized in mammals, studies in more complex plant genomes have so far been hampered by the absence of reference genome sequences. Barley is one of the economically most important cereals and has a genome size of 5.1 Gb. With the first high-quality genome reference assembly available for a Triticeae crop, we conducted a whole-genome assessment of pseudogenes on the barley genome. We identified, characterized and classified 89 440 gene fragments and pseudogenes scattered along the chromosomes, with occasional hotspots and higher densities at the chromosome ends. Full-length pseudogenes (11 015) have preferentially retained their exon-intron structure. Retrotransposition of processed mRNAs only plays a marginal role in their creation. However, the distribution of retroposed pseudogenes reflects the Rabl configuration of barley chromosomes and thus hints at founding mechanisms. While parent genes related to the defense-response were found to be under-represented in cultivated barley, we detected several defense-related pseudogenes in wild barley accessions. The percentage of transcriptionally active pseudogenes is 7.2%, and these may potentially adopt new regulatory roles.The barley genome is rich in pseudogenes and small gene fragments mainly located towards chromosome tips or as tandemly repeated units. Our results indicate non-random duplication and pseudogenization preferences and improve our understanding of the dynamics of gene birth and death in large plant genomes and the mechanisms that lead to evolutionary innovations.
Topics: Chromosome Mapping; Chromosomes, Plant; Gene Duplication; Genes, Plant; Hordeum; Multigene Family; Pseudogenes; Selection, Genetic; Synteny
PubMed: 29205595
DOI: 10.1111/tpj.13794 -
Yi Chuan = Hereditas Jan 2015Pseudogene is a DNA fragment with high sequence similarity to the corresponding functional gene. Because of accumulation of multiple mutations, pseudogenes have lost... (Review)
Review
Pseudogene is a DNA fragment with high sequence similarity to the corresponding functional gene. Because of accumulation of multiple mutations, pseudogenes have lost their original functions. Previous studies indicated that pseudogenes are dysfunctional relatives of the corresponding functional genes, and are noises in the process of genome evolution. However, with the development of molecular biotechnologies, more and more studies have demonstrated that pseudogenes possess important biologic functions. For example, some pseudogene could regulate the expression of functional genes by competitively binding to the miRNAs, some could produce endogenous small interference RNAs to negatively regulate the expression of functional genes, and some even could encode functional proteins. In this review, we summarize the recent research progresses of pseudogenes through four aspects: the classification, identification, function, and particularly the roles in cancers.
Topics: Animals; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Pseudogenes; Transcription, Genetic
PubMed: 25608808
DOI: 10.16288/j.yczz.2015.01.002 -
Molecular Biology and Evolution Jul 2022Prokaryotic genomes are usually densely packed with intact and functional genes. However, in certain contexts, such as after recent ecological shifts or extreme...
Prokaryotic genomes are usually densely packed with intact and functional genes. However, in certain contexts, such as after recent ecological shifts or extreme population bottlenecks, broken and nonfunctional gene fragments can quickly accumulate and form a substantial fraction of the genome. Identification of these broken genes, called pseudogenes, is a critical step for understanding the evolutionary forces acting upon, and the functional potential encoded within, prokaryotic genomes. Here, we present Pseudofinder, an open-source software dedicated to pseudogene identification and analysis in bacterial and archaeal genomes. We demonstrate that Pseudofinder's multi-pronged, reference-based approach can detect a wide variety of pseudogenes, including those that are highly degraded and typically missed by gene-calling pipelines, as well newly formed pseudogenes containing only one or a few inactivating mutations. Additionally, Pseudofinder can detect genes that lack inactivating substitutions but experiencing relaxed selection. Implementation of Pseudofinder in annotation pipelines will allow more precise estimations of the functional potential of sequenced microbes, while also generating new hypotheses related to the evolutionary dynamics of bacterial and archaeal genomes.
Topics: Bacteria; Genome, Archaeal; Prokaryotic Cells; Pseudogenes; Software
PubMed: 35801562
DOI: 10.1093/molbev/msac153 -
Genes & Genomics Jun 2020Pseudogenes have been known as non-functional molecular relics developed from inactivated genomic mutations while evolution. However, they have a various function at... (Review)
Review
Pseudogenes have been known as non-functional molecular relics developed from inactivated genomic mutations while evolution. However, they have a various function at distinct molecular stages (DNA, RNA and protein) in different biological events including in cancer and associated with parental-gene-dependently and parental-gene independently. The interactions of pseudogenes with ancestor genes or other genes alter in their sequences and transcriptional processes. Pseudogene of RNA sequences have multiple functions in post-transcriptional activities as antisense RNAs, endogenous small-interference RNAs, and competing endogenous RNAs. Moreover, it also plays vital roles in controlling of its parent genes and other pseudogenes transcribing into RNA. Pseudogene transcripts make small interfering RNA or decline cellular miRNA level. The current review focuses on pseudogene functional signature in human genome by regulating the gene expression.
Topics: Animals; Evolution, Molecular; Humans; Pseudogenes; RNA, Untranslated
PubMed: 32277362
DOI: 10.1007/s13258-020-00935-7 -
Advances in Experimental Medicine and... 2018Competing endogenous RNAs (ceRNAs) are kinds of RNAs that regulate each other at post-transcription level through competing for miRNA regulators. CeRNA-ceRNA networks... (Review)
Review
Competing endogenous RNAs (ceRNAs) are kinds of RNAs that regulate each other at post-transcription level through competing for miRNA regulators. CeRNA-ceRNA networks provide another type of function for protein-coding mRNAs, which link non-coding RNAs such as miRNA, long non-coding RNA, pseudogenes and circular RNAs. In this chapter, we will introduce the definition of ceRNAs, mainly provide the computational method to predict ceRNA interactions in general condition and complex diseases. In addition, we also illustrated several computational methods that are commonly used to identify the perturbed ceRNA networks in human diseases compared to normal conditions. Finally, we also summarized the principles of methods that integrated ceRNA theory to identify human disease biomarkers. Understanding of RNA-RNA crosstalk will provide significant insights into gene regulatory network that has been implicated in human development and/or diseases.
Topics: Disease; Gene Regulatory Networks; Humans; MicroRNAs; Pseudogenes; RNA; RNA, Circular; RNA, Long Noncoding; RNA, Messenger
PubMed: 30191491
DOI: 10.1007/978-981-13-0719-5_10 -
Methods in Molecular Biology (Clifton,... 2021Presence of pseudogenes is a dreadful issue in next generation sequencing (NGS), because their contamination can interfere with the detection of variants in the genuine... (Review)
Review
Presence of pseudogenes is a dreadful issue in next generation sequencing (NGS), because their contamination can interfere with the detection of variants in the genuine gene and generate false positive and false negative variants.In this chapter we focus on issues related to the application of NGS strategies for analysis of genes with pseudogenes in a clinical setting. The degree to which a pseudogene impacts the ability to accurately detect and map variants in its parent gene depends on the degree of similarity (homology) with the parent gene itself. Hereby, target enrichment and mapping strategies are crucial factors to avoid "contaminating" pseudogene sequences. For target enrichment, we describe advantages and disadvantages of PCR- and capture-based strategies. For mapping strategies, we discuss crucial parameters that need to be considered to accurately distinguish sequences of functional genes from pseudogenic sequences. Finally, we discuss some examples of genes associated with Mendelian disorders, for which interesting NGS approaches are described to avoid interference with pseudogene sequences.
Topics: Base Sequence; Data Analysis; Electrophoresis, Capillary; Genes, BRCA1; Genes, Neurofibromatosis 1; High-Throughput Nucleotide Sequencing; Humans; INDEL Mutation; Intercellular Signaling Peptides and Proteins; Mismatch Repair Endonuclease PMS2; Molecular Diagnostic Techniques; Multiplex Polymerase Chain Reaction; Oligonucleotide Probes; Polymorphism, Single Nucleotide; Pseudogenes; Reverse Transcriptase Polymerase Chain Reaction; TRPP Cation Channels
PubMed: 34165726
DOI: 10.1007/978-1-0716-1503-4_22 -
Tumour Biology : the Journal of the... Feb 2016Over the past decade, the importance of non-protein-coding functional elements in the human genome has emerged from the water and been identified as a key revelation in... (Review)
Review
Over the past decade, the importance of non-protein-coding functional elements in the human genome has emerged from the water and been identified as a key revelation in post-genomic biology. Since the completion of the ENCODE (Encyclopedia of DNA Elements) and FANTOM (Functional Annotation of Mammals) project, tens of thousands of pseudogenes as well as numerous long non-coding RNA (lncRNA) genes were identified. However, while pseudogenes were initially regarded as non-functional relics littering the human genome during evolution, recent studies have revealed that they play critical roles at multiple levels in diverse physiological and pathological processes, especially in cancer through parental-gene-dependent or parental-gene-independent regulation. Herein, we review the current knowledge of pseudogenes and synthesize the nascent evidence for functional properties and regulatory modalities exerted by pseudogene-transcribed RNAs in human cancers and prospect the potential as molecular signatures in cancer reclassification and tailored therapy.
Topics: Animals; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Pseudogenes; RNA
PubMed: 26662308
DOI: 10.1007/s13277-015-4482-z -
Journal of Medical Genetics Jan 2015Pseudogenes were initially regarded as non-functional genomic fossils resulted from inactivating gene mutations during evolution. However, later studies revealed that... (Review)
Review
Pseudogenes were initially regarded as non-functional genomic fossils resulted from inactivating gene mutations during evolution. However, later studies revealed that they play a plethora of roles at multiple levels (DNA, RNA and/or protein) in diverse physiological and pathological processes, especially in cancer, both parental-gene-dependently and parental-gene-independently. Pseudogenes can interact with parental genes or other gene loci, leading to alteration in their sequences and/or transcriptional activities. Pseudogene-derived RNAs play multifaceted roles in post-transcriptional regulation as antisense RNAs, endogenous small-interference RNAs, competing endogenous RNAs and so on. Pseudogenic proteins can mirror, mimic or interfere with the functions of their parental counterparts. Herein, we discuss the general aspects (origination, classification, identification) of pseudogenes, focus on their multiple functions in cancer pathogenesis and prospect the potentials they hold as molecular signatures assisting in cancer reclassification and tailored therapy.
Topics: DNA, Intergenic; Humans; Models, Genetic; Mutation; Neoplasms; Pseudogenes; RNA, Antisense
PubMed: 25391452
DOI: 10.1136/jmedgenet-2014-102785 -
Cells Nov 2020Ferritin, the principal intracellular iron-storage protein localized in the cytoplasm, nucleus, and mitochondria, plays a major role in iron metabolism. The encoding... (Review)
Review
Ferritin, the principal intracellular iron-storage protein localized in the cytoplasm, nucleus, and mitochondria, plays a major role in iron metabolism. The encoding ferritin genes are members of a multigene family that includes some pseudogenes. Even though pseudogenes have been initially considered as relics of ancient genes or junk DNA devoid of function, their role in controlling gene expression in normal and transformed cells has recently been re-evaluated. Numerous studies have revealed that some pseudogenes compete with their parental gene for binding to the microRNAs (miRNAs), while others generate small interference RNAs (siRNAs) to decrease functional gene expression, and still others encode functional mutated proteins. Consequently, pseudogenes can be considered as actual master regulators of numerous biological processes. Here, we provide a detailed classification and description of the structural features of the ferritin pseudogenes known to date and review the recent evidence on their mutual interrelation within the complex regulatory network of the ferritin gene family.
Topics: Animals; Ferritins; Gene Expression; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; MicroRNAs; Neoplasms; Oxidoreductases; Pseudogenes; RNA, Small Interfering
PubMed: 33260500
DOI: 10.3390/cells9122554 -
Nucleic Acids Research Jan 2023The HUGO Gene Nomenclature Committee (HGNC) assigns unique symbols and names to human genes. The HGNC database (www.genenames.org) currently contains over 43 000...
The HUGO Gene Nomenclature Committee (HGNC) assigns unique symbols and names to human genes. The HGNC database (www.genenames.org) currently contains over 43 000 approved gene symbols, over 19 200 of which are assigned to protein-coding genes, 14 000 to pseudogenes and nearly 9000 to non-coding RNA genes. The public website, www.genenames.org, displays all approved nomenclature within Symbol Reports that contain data curated by HGNC nomenclature advisors and links to related genomic, clinical, and proteomic information. Here, we describe updates to our resource, including improvements to our search facility and new download features.
Topics: Humans; Databases, Genetic; Genome; Genomics; Proteomics; Pseudogenes; Terminology as Topic
PubMed: 36243972
DOI: 10.1093/nar/gkac888