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BMC Genomics 2015Over the last decade, methods have been developed for the reconstruction of gene trees that take into account the species tree. Many of these methods have been based on...
Over the last decade, methods have been developed for the reconstruction of gene trees that take into account the species tree. Many of these methods have been based on the probabilistic duplication-loss model, which describes how a gene-tree evolves over a species-tree with respect to duplication and losses, as well as extension of this model, e.g., the DLRS (Duplication, Loss, Rate and Sequence evolution) model that also includes sequence evolution under relaxed molecular clock. A disjoint, almost as recent, and very important line of research has been focused on non protein-coding, but yet, functional DNA. For instance, DNA sequences being pseudogenes in the sense that they are not translated, may still be transcribed and the thereby produced RNA may be functional.
Topics: DNA; Evolution, Molecular; Gene Duplication; Phylogeny; Pseudogenes
PubMed: 26449131
DOI: 10.1186/1471-2164-16-S10-S12 -
Scientific Reports Apr 2018The diversity of the T cell receptor (TCR) complementarity determining region 3 (CDR3) repertoire is the result of random combinations, insertions and deletions during...
The diversity of the T cell receptor (TCR) complementarity determining region 3 (CDR3) repertoire is the result of random combinations, insertions and deletions during recombination of the germline V, D and J gene fragments. During evolution, some human TCR beta chain variable (TRBV) pseudogenes have been retained. Many previous studies have focused on functional TRBV genes, while little attention has been given to TRBV pseudogenes. To describe the compositional characteristics of TRBV pseudogene rearrangements, we compared and analysed TRBV pseudogenes, TRBV open reading frames (ORFs) and functional TRBV genes via high-throughput sequencing of DNA obtained from the peripheral blood of 4 healthy volunteers and 4 patients. Our results revealed several differences in J and D gene usage. The V deletion distribution profile of the pseudogenes was significantly different from that of the ORFs and functional genes. In addition, arginine, lysine and cysteine were more frequently used in putative CDR3 pseudogene rearrangements, while functional rearrangements used more leucine. This study presents a comprehensive description of the compositional characteristics of peripheral TRBV pseudogene rearrangements, which will provide a reference for further research on TRBV pseudogenes.
Topics: Complementarity Determining Regions; Genes, T-Cell Receptor beta; Healthy Volunteers; High-Throughput Nucleotide Sequencing; Humans; Pseudogenes; Receptor-CD3 Complex, Antigen, T-Cell; Receptors, Antigen, T-Cell
PubMed: 29651132
DOI: 10.1038/s41598-018-24367-2 -
Genomics Jul 2021Pancreatic cancer, the most lethal malignant tumor, is notorious for its poor prognosis and metastatic potential. Non-coding RNAs (ncRNAs) are reported to play key roles...
Pancreatic cancer, the most lethal malignant tumor, is notorious for its poor prognosis and metastatic potential. Non-coding RNAs (ncRNAs) are reported to play key roles in cancer metastasis. In this study, miRNA and gene expression profiles between metastatic pancreatic cancer cell M8 and its parental cell BxPC.3 were determined. Using differential expression analysis, survival analysis, target gene prediction, pathway enrichment analysis, intersection analysis and correlation analysis, hsa-miR-30d-5p/GJA1 axis was identified as the most potential pathway involved in metastasis of pancreatic cancer. Subsequently, two upstream lncRNAs (HELLPAR and OIP-AS1) and four upstream pseudogenes (AC093616.1, AC009951.1, TMEM183B and PABPC1P4) of hsa-miR-30d-5p/GJA1 axis were predicted and were then identified via assessment of RNA-RNA expression relationship. Furthermore, CTNNA1, CTNNB1 and CTNND1 were regarded as three crucial molecules to be participated in hsa-miR-30d-5p/GJA1-mediated metastatic potential in pancreatic cancer. In conclusion, we established a novel lncRNA/pseudogene-hsa-miR-30d-5p-GJA1 regulatory network linked to metastasis of pancreatic cancer.
Topics: Connexin 43; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Pancreatic Neoplasms; Pseudogenes; RNA, Long Noncoding; Transcriptome
PubMed: 33839271
DOI: 10.1016/j.ygeno.2021.04.013 -
Genome Biology Oct 2017Genome duplication has played a pivotal role in the evolution of many eukaryotic lineages, including the vertebrates. A relatively recent vertebrate genome duplication...
BACKGROUND
Genome duplication has played a pivotal role in the evolution of many eukaryotic lineages, including the vertebrates. A relatively recent vertebrate genome duplication is that in Xenopus laevis, which resulted from the hybridization of two closely related species about 17 million years ago. However, little is known about the consequences of this duplication at the level of the genome, the epigenome, and gene expression.
RESULTS
The X. laevis genome consists of two subgenomes, referred to as L (long chromosomes) and S (short chromosomes), that originated from distinct diploid progenitors. Of the parental subgenomes, S chromosomes have degraded faster than L chromosomes from the point of genome duplication until the present day. Deletions appear to have the largest effect on pseudogene formation and loss of regulatory regions. Deleted regions are enriched for long DNA repeats and the flanking regions have high alignment scores, suggesting that non-allelic homologous recombination has played a significant role in the loss of DNA. To assess innovations in the X. laevis subgenomes we examined p300-bound enhancer peaks that are unique to one subgenome and absent from X. tropicalis. A large majority of new enhancers comprise transposable elements. Finally, to dissect early and late events following interspecific hybridization, we examined the epigenome and the enhancer landscape in X. tropicalis × X. laevis hybrid embryos. Strikingly, young X. tropicalis DNA transposons are derepressed and recruit p300 in hybrid embryos.
CONCLUSIONS
The results show that erosion of X. laevis genes and functional regulatory elements is associated with repeats and non-allelic homologous recombination and furthermore that young repeats have also contributed to the p300-bound regulatory landscape following hybridization and whole-genome duplication.
Topics: Animals; Chromatin; Chromosome Deletion; DNA Transposable Elements; Enhancer Elements, Genetic; Epigenesis, Genetic; Gene Expression; Genome; Hybridization, Genetic; Pseudogenes; Tetraploidy; Xenopus; Xenopus laevis
PubMed: 29065907
DOI: 10.1186/s13059-017-1335-7 -
BMC Cancer Sep 2020There is growing evidence that pseudogenes may serve as prognostic biomarkers in several cancers. The present study was designed to develop and validate an accurate and...
BACKGROUND
There is growing evidence that pseudogenes may serve as prognostic biomarkers in several cancers. The present study was designed to develop and validate an accurate and robust pseudogene pairs-based signature for the prognosis of hepatocellular carcinoma (HCC).
METHODS
RNA-sequencing data from 374 HCC patients with clinical follow-up information were obtained from the Cancer Genome Atlas (TCGA) database and used in this study. Survival-related pseudogene pairs were identified, and a signature model was constructed by Cox regression analysis (univariate and least absolute shrinkage and selection operator). All individuals were classified into high- and low-risk groups based on the optimal cutoff. Subgroups analysis of the novel signature was conducted and validated in an independent cohort. Pearson correlation analyses were carried out between the included pseudogenes and the protein-coding genes based on their expression levels. Enrichment analysis was performed to predict the possible role of the pseudogenes identified in the signature.
RESULTS
A 19-pseudogene pair signature, which included 21 pseudogenes, was established. Patients in high-risk group demonstrated an increased the risk of adverse prognosis in the TCGA cohort and the external cohort (all P < 0.001). The novel pseudogene signature was independent of other conventional clinical variables used for survival prediction in HCC patients in the two cohorts revealed by the multivariate Cox regression analysis (all P < 0.001). Subgroup analysis further demonstrated the diagnostic value of the signature across different stages, grades, sexes, and age groups. The C-index of the prognostic signature was 0.761, which was not only higher than that of several previous risk models but was also much higher than that of a single age, sex, grade, and stage risk model. Furthermore, functional analysis revealed that the potential biological mechanisms mediated by these pseudogenes are primarily involved in cytokine receptor activity, T cell receptor signaling, chemokine signaling, NF-κB signaling, PD-L1 expression, and the PD-1 checkpoint pathway in cancer.
CONCLUSION
The novel proposed and validated pseudogene pair-based signature may serve as a valuable independent prognostic predictor for predicting survival of patients with HCC.
Topics: Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Survival Analysis
PubMed: 32938429
DOI: 10.1186/s12885-020-07391-2 -
Uirusu 2020RNA viruses do not need to take the form of DNAs, and RNAs alone complete their replication cycles. On the other hand, since the 1970s, it has been known that DNA... (Review)
Review
RNA viruses do not need to take the form of DNAs, and RNAs alone complete their replication cycles. On the other hand, since the 1970s, it has been known that DNA fragments derived from RNA viruses can be detected in RNA virus-infected cells. Furthermore, in this decade, it has become clear that the eukaryotic genomes contain genetic sequences derived from non-retroviral RNA viruses. The DNA sequences derived from these RNA viruses are thought to be generatedby using a transposable mechanism of retrotransposon, such as LINE-1. Many endogenous RNA viral sequences are formed by the same mechanism as processed pseudogenes in eukaryotic cells, but the significance of the production of RNA viral "pseudogenes " in infected cells has not been elucidated. We have discovered endogenous bornavirus-like elements (EBLs), which derived from a negative-sense, single-stranded RNA virus, Bornaviruses, and have studied the evolution and function of EBLs in host animals. The analysis of EBLs provides us a clue to unravel the history of host-RNA virus coexistence. In this review, I overview about the function of endogenous RNA virus sequences, especially EBLs in mammalian genomes, and discuss the significance of endogenization of RNA viruses as viral pseudogenes in evolution.
Topics: Animals; Bornaviridae; Genome; Pseudogenes; RNA; RNA Viruses; RNA, Viral
PubMed: 33967113
DOI: 10.2222/jsv.70.49 -
Genome Research Oct 2018Despite the importance of duplicate genes for evolutionary adaptation, accurate gene annotation is often incomplete, incorrect, or lacking in regions of segmental...
Despite the importance of duplicate genes for evolutionary adaptation, accurate gene annotation is often incomplete, incorrect, or lacking in regions of segmental duplication. We developed an approach combining long-read sequencing and hybridization capture to yield full-length transcript information and confidently distinguish between nearly identical genes/paralogs. We used biotinylated probes to enrich for full-length cDNA from duplicated regions, which were then amplified, size-fractionated, and sequenced using single-molecule, long-read sequencing technology, permitting us to distinguish between highly identical genes by virtue of multiple paralogous sequence variants. We examined 19 gene families as expressed in developing and adult human brain, selected for their high sequence identity (average >99%) and overlap with human-specific segmental duplications (SDs). We characterized the transcriptional differences between related paralogs to better understand the birth-death process of duplicate genes and particularly how the process leads to gene innovation. In 48% of the cases, we find that the expressed duplicates have changed substantially from their ancestral models due to novel sites of transcription initiation, splicing, and polyadenylation, as well as fusion transcripts that connect duplication-derived exons with neighboring genes. We detect unannotated open reading frames in genes currently annotated as pseudogenes, while relegating other duplicates to nonfunctional status. Our method significantly improves gene annotation, specifically defining full-length transcripts, isoforms, and open reading frames for new genes in highly identical SDs. The approach will be more broadly applicable to genes in structurally complex regions of other genomes where the duplication process creates novel genes important for adaptive traits.
Topics: Brain; Evolution, Molecular; Gene Duplication; Gene Expression Profiling; Humans; Molecular Sequence Annotation; Multigene Family; Open Reading Frames; Pseudogenes; Segmental Duplications, Genomic; Sequence Analysis, DNA; Sequence Analysis, RNA
PubMed: 30228200
DOI: 10.1101/gr.237610.118 -
Journal of Clinical Laboratory Analysis May 2017To examine the accuracy of fetal RHD genotype and RHD pseudogene determination in a multiethnical population.
OBJECTIVE
To examine the accuracy of fetal RHD genotype and RHD pseudogene determination in a multiethnical population.
METHODS
Prospective study involving D-negative pregnant women. Cell-free DNA was extracted from 1 ml of maternal plasma by an automated system (MagNA Pure Compact, Roche) and real-time PCR was performed in triplicate targeting the RHD gene exons 5 and 7. Inconclusive samples underwent RHD pseudogene testing by real-time PCR analysis employing novel primers and probe.
RESULTS
A positive result was observed in 128/185 (69.2%) samples and negative in 50 (27.0%). Umbilical cord blood phenotype confirmed all cases with a positive or negative PCR result. Seven (3.8%) cases were found inconclusive (exon 7 amplification only) and RHD pseudogene testing with both conventional and real-time PCR demonstrated a positive result in five of them, while two samples were also RHD pseudogene negative.
CONCLUSION
Real-time PCR targeting RHD exons 5 and 7 simultaneously in maternal plasma is an accurate method for the diagnosis of fetal D genotype in our population. The RHD pseudogene real-time PCR assay is feasible and is particularly useful in populations with a high prevalence of this allele.
Topics: Adult; DNA; Female; Genotyping Techniques; Humans; Pregnancy; Prenatal Diagnosis; Prospective Studies; Pseudogenes; Rh-Hr Blood-Group System; Sensitivity and Specificity; Young Adult
PubMed: 27595845
DOI: 10.1002/jcla.22052 -
Bioscience Reports Jul 2021Long noncoding RNAs (lncRNAs) play critical factors in tumor progression and are ectopically expressed in malignant tumors. Until now, lncRNA pituitary...
Long noncoding RNAs (lncRNAs) play critical factors in tumor progression and are ectopically expressed in malignant tumors. Until now, lncRNA pituitary tumor-transforming 3, pseudogene (PTTG3P) biological function in colorectal cancer (CRC) further needs to be clarified. qRT-PCR was used to measure the PTTG3P level and CCK-8, glucose uptake, lactate assay, adenosine triphosphate (ATP) assay, extracellular acidification rate (ECAR) assay, and xenograft mice model were adopted to evaluate the glycolysis and proliferation, and macrophage polarization were determined in CRC cells. Xenograft experiments were utilized to analyze tumor growth. Ectopic expression of PTTG3P was involved in CRC and related to dismal prognosis. Through gain- and loss-of-function approaches, PTTG3P enhanced cell proliferation and glycolysis through YAP1. Further, LDHA knockdown or glycolysis inhibitor (2-deoxyglucose (2-DG), 3-BG) recovered from PTTG3P-induced proliferation. And PTTG3P overexpression could facilitate M2 polarization of macrophages. Silenced PTTG3P decreased the level of inflammatory cytokines TNF-α, IL-1β and IL-6, and low PTTG3P expression related with CD8+ T, NK, and TFH cell infiltration. Besides, hypoxia-inducible factor-1α (HIF1A) could increase PTTG3P expression by binding to the PTTG3P promoter region. Hypoxia-induced PTTG3P contributes to glycolysis and M2 phenotype of macrophage, which proposes a novel approach for clinical treatment.
Topics: Animals; Cell Proliferation; Colorectal Neoplasms; Cytokines; Databases, Genetic; Female; Gene Expression Regulation, Neoplastic; Glycolysis; HCT116 Cells; HT29 Cells; Humans; Inflammation Mediators; Male; Mice, Nude; Middle Aged; Phenotype; Pseudogenes; RNA, Long Noncoding; Signal Transduction; Tumor Burden; Tumor Hypoxia; Tumor Microenvironment; Tumor-Associated Macrophages; Mice
PubMed: 34132347
DOI: 10.1042/BSR20210764 -
Genes Jan 2023Most pseudogenes are generated when an RNA transcript is reverse-transcribed and integrated into the genome at a new location. Pseudogenes are often considered as an...
Most pseudogenes are generated when an RNA transcript is reverse-transcribed and integrated into the genome at a new location. Pseudogenes are often considered as an imperfect and silent copy of a functional gene because of the accumulation of numerous mutations in their sequence. Here we report the presence of , a retrotransposed pseudogene in the mouse genome, which has no disruptions in its coding sequence. We show that this pseudogene is mainly transcribed in testis and can produce a PHF8-PS protein in vivo. As the PHF8-PS protein has a well-conserved JmjC domain, we characterized its enzymatic activity and show that PHF8-PS does not have the intrinsic capability to demethylate H3K9me2 in vitro compared to the parental PHF8 protein. Surprisingly, PHF8-PS does not localize in the nucleus like PHF8, but rather is mostly located at the cytoplasm. Finally, our proteomic analysis of PHF8-PS-associated proteins revealed that PHF8-PS interacts not only with mitochondrial proteins, but also with prefoldin subunits (PFDN proteins) that deliver unfolded proteins to the cytosolic chaperonin complex implicated in the folding of cytosolic proteins. Together, our findings highlighted PHF8-PS as a new pseudogene-derived protein with distinct molecular functions from PHF8.
Topics: Male; Animals; Mice; Transcription Factors; Pseudogenes; Proteomics; Histone Demethylases; Histones
PubMed: 36672913
DOI: 10.3390/genes14010172