-
Experimental Hematology Nov 2021Pseudogenes are DNA regions comprising defective copies of functional genes, the majority of which were generated by RNA- or DNA-level duplications. They exist across... (Review)
Review
Pseudogenes are DNA regions comprising defective copies of functional genes, the majority of which were generated by RNA- or DNA-level duplications. They exist across almost all forms of life and account for about one-quarter of the annotated genes in the human genome. Although these have been considered nonfunctional for decades, a growing number of pseudogenes have been found to be transcribed and to play crucial regulatory roles. Accumulating evidence indicates that they regulate gene expression through molecular interactions at the protein, RNA, and DNA levels. However, pseudogenes are often excluded in multiple genomewide analyses and functional screening, and their biological activities remain to be systematically disclosed. Here, we summarize the features of and progress of research on pseudogenes, in addition to discussing what is unknown about these genetic elements. Our previous findings, together with evidence of their poor conservation, prompted us to propose that pseudogenes may contribute to primate- or human-specific regulation, especially in hematopoiesis.
Topics: Animals; Gene Expression Regulation, Developmental; Gene Expression Regulation, Leukemic; Hematopoiesis; Humans; Leukemia; Pseudogenes
PubMed: 34517065
DOI: 10.1016/j.exphem.2021.09.001 -
Current Opinion in Microbiology Feb 2015Pseudogenes are defined as fragments of once-functional genes that have been silenced by one or more nonsense, frameshift or missense mutations. Despite continuing... (Review)
Review
Pseudogenes are defined as fragments of once-functional genes that have been silenced by one or more nonsense, frameshift or missense mutations. Despite continuing increases in the speed of sequencing and annotating bacterial genomes, the identification and categorisation of pseudogenes remains problematic. Even when identified, pseudogenes are considered to be rare and tend to be ignored. On the contrary, pseudogenes are surprisingly prevalent and can persist for long evolutionary time periods, representing a record of once-functional genetic characteristics. Most importantly, pseudogenes provide an insight into prokaryotic evolutionary history as a record of phenotypic traits that have been lost. Focusing on the intracellular and symbiotic bacteria in which pseudogenes predominate, this review discusses the importance of identifying pseudogenes to fully understand the abilities of bacteria, and to understand prokaryotes within their evolutionary context.
Topics: Bacteria; Evolution, Molecular; Pseudogenes
PubMed: 25461580
DOI: 10.1016/j.mib.2014.11.012 -
Journal of Cellular and Molecular... Jan 2017The concept of competitive endogenous RNA (ceRNA) was first proposed by Salmena and colleagues. Evidence suggests that pseudogene RNAs can act as a 'sponge' through... (Review)
Review
The concept of competitive endogenous RNA (ceRNA) was first proposed by Salmena and colleagues. Evidence suggests that pseudogene RNAs can act as a 'sponge' through competitive binding of common miRNA, releasing or attenuating repression through sequestering miRNAs away from parental mRNA. In theory, ceRNAs refer to all transcripts such as mRNA, tRNA, rRNA, long non-coding RNA, pseudogene RNA and circular RNA, because all of them may become the targets of miRNA depending on spatiotemporal situation. As binding of miRNA to the target RNA is not 100% complementary, it is possible that one miRNA can bind to multiple target RNAs and vice versa. All RNAs crosstalk through competitively binding to miRNAvia miRNA response elements (MREs) contained within the RNA sequences, thus forming a complex regulatory network. The ratio of a subset of miRNAs to the corresponding number of MREs determines repression strength on a given mRNA translation or stability. An increase in pseudogene RNA level can sequester miRNA and release repression on the parental gene, leading to an increase in parental gene expression. A massive number of transcripts constitute a complicated network that regulates each other through this proposed mechanism, though some regulatory significance may be mild or even undetectable. It is possible that the regulation of gene and pseudogene expression occurring in this manor involves all RNAs bearing common MREs. In this review, we will primarily discuss how pseudogene transcripts regulate expression of parental genes via ceRNA network and biological significance of regulation.
Topics: Animals; Gene Expression; Gene Regulatory Networks; Humans; Pseudogenes; RNA; Response Elements
PubMed: 27561207
DOI: 10.1111/jcmm.12952 -
International Journal of Molecular... Apr 2018Noncoding RNAs (ncRNAs) constitute the majority of the human transcribed genome. This largest class of RNA transcripts plays diverse roles in a multitude of cellular... (Review)
Review
Noncoding RNAs (ncRNAs) constitute the majority of the human transcribed genome. This largest class of RNA transcripts plays diverse roles in a multitude of cellular processes, and has been implicated in many pathological conditions, especially cancer. The different subclasses of ncRNAs include microRNAs, a class of short ncRNAs; and a variety of long ncRNAs (lncRNAs), such as lincRNAs, antisense RNAs, pseudogenes, and circular RNAs. Many studies have demonstrated the involvement of these ncRNAs in competitive regulatory interactions, known as competing endogenous RNA (ceRNA) networks, whereby lncRNAs can act as microRNA decoys to modulate gene expression. These interactions are often interconnected, thus aberrant expression of any network component could derail the complex regulatory circuitry, culminating in cancer development and progression. Recent integrative analyses have provided evidence that new computational platforms and experimental approaches can be harnessed together to distinguish key ceRNA interactions in specific cancers, which could facilitate the identification of robust biomarkers and therapeutic targets, and hence, more effective cancer therapies and better patient outcome and survival.
Topics: Biomarkers, Tumor; Carcinogenesis; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasms; Pseudogenes; RNA; RNA Transport; RNA, Circular; RNA, Long Noncoding
PubMed: 29702599
DOI: 10.3390/ijms19051310 -
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 -
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 -
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 -
International Journal of Molecular... Nov 2016Pseudogenes are paralogs generated from ancestral functional genes (parents) during genome evolution, which contain critical defects in their sequences, such as lacking... (Review)
Review
Pseudogenes are paralogs generated from ancestral functional genes (parents) during genome evolution, which contain critical defects in their sequences, such as lacking a promoter, having a premature stop codon or frameshift mutations. Generally, pseudogenes are functionless, but recent evidence demonstrates that some of them have potential roles in regulation. The majority of pseudogenes are generated from functional progenitor genes either by gene duplication (duplicated pseudogenes) or retro-transposition (processed pseudogenes). Pseudogenes are primarily identified by comparison to their parent genes. Bioinformatics tools for pseudogene prediction have been developed, among which PseudoPipe, PSF and Shiu's pipeline are publicly available. We compared these three tools using the well-annotated genome and its known 924 pseudogenes as a test data set. PseudoPipe and Shiu's pipeline identified ~80% of pseudogenes, of which 94% were shared, while PSF failed to generate adequate results. A need for improvement of the bioinformatics tools for pseudogene prediction accuracy in plant genomes was thus identified, with the ultimate goal of improving the quality of genome annotation in plants.
Topics: Computational Biology; Gene Duplication; Genome, Plant; Pseudogenes
PubMed: 27916797
DOI: 10.3390/ijms17121991 -
Microbial Genomics Oct 2022Whole-genome sequence analyses have significantly contributed to the understanding of virulence and evolution of the complex (MTBC), the causative pathogens of...
Whole-genome sequence analyses have significantly contributed to the understanding of virulence and evolution of the complex (MTBC), the causative pathogens of tuberculosis. Most MTBC evolutionary studies are focused on single nucleotide polymorphisms and deletions, but rare studies have evaluated gene content, whereas none has comprehensively evaluated pseudogenes. Accordingly, we describe an extensive study focused on quantifying and predicting possible functions of MTBC and pseudogenes. Using NCBI's PGAP-detected pseudogenes, we analysed 25 837 pseudogenes from 158 MTBC and strains and combined transcriptomics and proteomics of H37Rv to gain insights about pseudogenes' expression. Our results indicate significant variability concerning rate and conservancy of predicted pseudogenes among different ecotypes and lineages of tuberculous mycobacteria and pseudogenization of important virulence factors and genes of the metabolism and antimicrobial resistance/tolerance. We show that predicted pseudogenes contribute considerably to MTBC genetic diversity at the population level. Moreover, the transcription machinery of can fully transcribe most pseudogenes, indicating intact promoters and recent pseudogene evolutionary emergence. Proteomics of and close evaluation of mutational lesions driving pseudogenization suggest that few predicted pseudogenes are likely capable of neofunctionalization, nonsense mutation reversal, or phase variation, contradicting the classical definition of pseudogenes. Such findings indicate that genome annotation should be accompanied by proteomics and protein function assays to improve its accuracy. While indels and insertion sequences are the main drivers of the observed mutational lesions in these species, population bottlenecks and genetic drift are likely the evolutionary processes acting on pseudogenes' emergence over time. Our findings unveil a new perspective on MTBC's evolution and genetic diversity.
Topics: Anti-Infective Agents; Codon, Nonsense; DNA Transposable Elements; Mycobacterium tuberculosis; Pseudogenes; Virulence Factors; Drug Resistance, Bacterial
PubMed: 36250787
DOI: 10.1099/mgen.0.000876