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Pseudogenes can provide valuable insight into the evolutionary history of genomes which may be difficult to determine based on the examination of functional loci alone. This study presents the results of a comprehensive, two-stage genome-wide investigation into the identification and characterization of pseudogenes in Fusarium graminearum , the main causal agent of wheat head blight. By analyzing sequence homology between non-coding regions of the genome and predicted protein sequences, regions with homology to putative paralogous functional sequences were identified. These regions were characterized in terms of their matching sequence structure and position. Most of the pseudogenes identified were mapped within the fast-evolving genomic compartment and were derived from transposition events. The number of processed and putatively retroposed pseudogenes was found to be comparable. The low number of identified pseudogenes is consistent with the low number of gene duplicates in F. graminearum . No compelling evidence was found to suggest that pseudogene formation can be explained by evolutionary accidents during gene family expansion, nor that it is caused by RIP-associated mutagenic events. Notably, approximately one-third (144 of 436) of the pseudogenes were found to overlap with the untranslated or intron sequences of functional loci, suggesting that they could potentially be transcribed. Using comparative Fusarium genomics, we identified genomic regions with homology to genes lacking functional orthologues in F. graminearum . These were investigated as putative unitary pseudogenes, some of which had lost their original functions completely after the radiation of F. graminearum . Interestingly, the orthologous loci matching parents of the 18 loss-of-function pseudogenes showed homology to domains previously identified in proteins involved in pathogenesis.

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.

Nuclear mitochondrial pseudogenes (numts) are nonfunctional copies of mtDNA in the nucleus that have been found in major clades of eukaryotic organisms. They can be easily coamplified with orthologous mtDNA by using conserved universal primers; however, this is especially problematic for DNA barcoding, which attempts to characterize all living organisms by using a short fragment of the mitochondrial cytochrome c oxidase I (COI) gene. Here, we study the effect of numts on DNA barcoding based on phylogenetic and barcoding analyses of numt and mtDNA sequences in two divergent lineages of arthropods: grasshoppers and crayfish. Single individuals from both organisms have numts of the COI gene, many of which are highly divergent from orthologous mtDNA sequences, and DNA barcoding analysis incorrectly overestimates the number of unique species based on the standard metric of 3% sequence divergence. Removal of numts based on a careful examination of sequence characteristics, including indels, in-frame stop codons, and nucleotide composition, drastically reduces the incorrect inferences of the number of unique species, but even such rigorous quality control measures fail to identify certain numts. We also show that the distribution of numts is lineage-specific and the presence of numts cannot be known a priori. Whereas DNA barcoding strives for rapid and inexpensive generation of molecular species tags, we demonstrate that the presence of COI numts makes this goal difficult to achieve when numts are prevalent and can introduce serious ambiguity into DNA barcoding.

Pseudogenes are defined as “non-functional” copies of corresponding parent genes. The cognition of pseudogenes continues to be refreshed through accumulating and updating research findings. Previous studies have predominantly focused on mammals, but pseudogenes have received relatively less attention in the field of microbiology. Given the increasing recognition on the importance of pseudogenes, in this review, we focus on several aspects of microorganism pseudogenes, including their classification and characteristics, their generation and fate, their identification, their abundance and distribution, their impact on virulence, their ability to recombine with functional genes, the extent to which some pseudogenes are transcribed and translated, and the relationship between pseudogenes and viruses. By summarizing and organizing the latest research progress, this review will provide a comprehensive perspective and improved understanding on pseudogenes in microorganisms. Key points • Concept, classification and characteristics, identification and databases, content, and distribution of microbial pseudogenes are presented. • How pseudogenization contribute to pathogen virulence is highlighted. • Pseudogenes with potential functions in microorganisms are discussed.

Pseudogenes were initially regarded as \"nonfunctional\" genomic elements that did not have protein-coding abilities due to several endogenous inactivating mutations. Although pseudogenes are widely expressed in prokaryotes and eukaryotes, for decades, they have been largely ignored and classified as gene \"junk\" or \"relics\". With the widespread availability of high-throughput sequencing analysis, especially omics technologies, knowledge concerning pseudogenes has substantially increased. Pseudogenes are evolutionarily conserved and derive primarily from a mutation or retrotransposon, conferring the pseudogene with a \"gene repository\" role to store and expand genetic information. In contrast to previous notions, pseudogenes have a variety of functions at the DNA, RNA and protein levels for broadly participating in gene regulation to influence the development and progression of certain diseases, especially cancer. Indeed, some pseudogenes have been proven to encode proteins, strongly contradicting their \"trash\" identification, and have been confirmed to have tissue-specific and disease subtype-specific expression, indicating their own value in disease diagnosis. Moreover, pseudogenes have been correlated with the life expectancy of patients and exhibit great potential for future use in disease treatment, suggesting that they are promising biomarkers and therapeutic targets for clinical applications. In this review, we summarize the natural properties, functions, disease involvement and clinical value of pseudogenes. Although our knowledge of pseudogenes remains nascent, this field deserves more attention and deeper exploration.

We have optimized and extended the widely used annotation engine MAKER in order to better support plant genome annotation efforts. New features include better parallelization for large repeat-rich plant genomes, noncoding RNA annotation capabilities, and support for pseudogene identification. We have benchmarked the resulting software tool kit, MAKER-P, using the Arabidopsis (Arabidopsis thaliana) and maize (Zea mays) genomes. Here, we demonstrate the ability of the MAKER-P tool kit to automatically update, extend, and revise the Arabidopsis annotations in light of newly available data and to annotate pseudogenes and noncoding RNAs absent from The Arabidopsis Informatics Resource 10 build. Our results demonstrate that MAKER-P can be used to manage and improve the annotations of even Arabidopsis, perhaps the best-annotated plant genome. We have also installed and benchmarked MAKER-P on the Texas Advanced Computing Center. We show that this public resource can de novo annotate the entire Arabidopsis and maize genomes in less than 3 h and produce annotations of comparable quality to those of the current The Arabidopsis Information Resource 10 and maize V2 annotation builds.

Abstract 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.

Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.

Recent studies show that transcription of the mammalian genome is not only pervasive but also enormously complex. It is estimated that an average of 10 transcription units, the vast majority of which make long noncoding RNAs (lncRNAs), may overlap each traditional coding gene. These lncRNAs include not only antisense, intronic, and intergenic transcripts but also pseudogenes and retrotransposons. Do they universally have function, or are they merely transcriptional by-products of conventional coding genes? A glimpse into the molecular biology of multiple emerging lncRNA systems reveals the \"Wild West\" landscape of their functions and mechanisms and the key problems to solve in the years ahead toward understanding these intriguing macromolecules.