The Pseudogene DUXAP8 Promotes Colorectal Cancer Cell Proliferation, Invasion, and Migration by Inducing Epithelial-Mesenchymal Transition Through Interacting with EZH2 and H3K27me3
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Transcription factor pseudogenes have not been systematically studied before. Nuclear receptors (NRs) constitute one of the largest groups of transcription factors in animals (e.g., 48 NRs in human). The availability of whole-genome sequences enables a global inventory of the NR pseudogenes in a number of vertebrate model organisms. Here we identify the NR pseudogenes in 8 vertebrate organisms and make our results available online at http://www.pseudogene.org/nr. The assignments reveal that NR pseudogenes as a group have characteristics related to generation and distribution contrary to expectations derived from previous large-scale pseudogene studies. In particular, 1) despite its large size, the NR gene family has only a very small number of pseudogenes in each of the vertebrate genomes examined; 2) despite the low transcription levels of NR genes, except for one, all other NR pseudogenes identified in this study are retropseudogenes; and 3) no duplicated NR pseudogenes are found, contrary to the fact that the NR gene family was expanded through several waves of gene duplication events. Our analyses further reveal a number of interesting aspects of NR pseudogenes. Specifically, through careful sequence analysis, we identify remnant introns in 2 mouse retropseudogenes, ψRev-erbβ and ψLRH1. Generated from partially processed pre-mRNAs, they appear to be rare examples of highly unusual "semiprocessed" pseudogenes. Second, by comparing the genomic sequences, we uncover a pseudogene that is unique to the human lineage relative to chimpanzee. Generated by a recent duplication of a segment in the human genome, this pseudogene is a "duplicated–processed" pseudogene, belonging to a new pseudogene species. Finally, FXRβ was nonfunctionalized in the human lineage and thus appears to be an example of a rare unitary pseudogene. By comparing orthologous sequences, we dated the FXR–FXRβ duplication and the nonfunctionalization of FXRβ in primates.
Pseudogene
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Pseudogenes are homologous relatives of known genes that have lost their ability to function as a transcriptional unit. Three classes of pseudogenes are known to exist: duplicated pseudogenes; processed or retrotransposed pseudogenes; and unitary or disabled pseudogenes. Since pseudogenes may display a number of the characteristics of functional genes, they pose a unique set of problems for ab initio gene prediction. The ability to detect and differentiate pseudogenes from functional genes can be a difficult task. We present a comprehensive review of current approaches for pseudogene detection, highlighting difficulties in pseudogene differentiation.
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Pseudogene
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Pseudogene
Ribosomal protein
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Pseudogenes are fossil relatives of genes. Pseudogenes have long been thought of as junk DNAs, since they do not code proteins in normal tissues. Although most of the human pseudogenes do not have noticeable functions, ∼20% of them exhibit transcriptional activity. There has been evidence showing that some pseudogenes adopted functions as lncRNAs and work as regulators of gene expression. Furthermore, pseudogenes can even be reactivated in some conditions, such as cancer initiation. Some pseudogenes are transcribed in specific cancer types, and some are even translated into proteins as observed in several cancer cell lines. All the above have shown that pseudogenes could have functional roles or potentials in the genome. Evaluating the relationships between pseudogenes and their gene counterparts could help us reveal the evolutionary path of pseudogenes and associate pseudogenes with functional potentials. It also provides an insight into the regulatory networks involving pseudogenes with transcriptional and even translational activities.In this study, we develop a novel approach integrating graph analysis, sequence alignment and functional analysis to evaluate pseudogene-gene relationships, and apply it to human gene homologs and pseudogenes. We generated a comprehensive set of 445 pseudogene-gene (PGG) families from the original 3,281 gene families (13.56%). Of these 438 (98.4% PGG, 13.3% total) were non-trivial (containing more than one pseudogene). Each PGG family contains multiple genes and pseudogenes with high sequence similarity. For each family, we generate a sequence alignment network and phylogenetic trees recapitulating the evolutionary paths. We find evidence supporting the evolution history of olfactory family (both genes and pseudogenes) in human, which also supports the validity of our analysis method. Next, we evaluate these networks in respect to the gene ontology from which we identify functions enriched in these pseudogene-gene families and infer functional impact of pseudogenes involved in the networks. This demonstrates the application of our PGG network database in the study of pseudogene function in disease context.
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Pseudogenes,disabled copies of functional genes,are structurally similar to its parantal genes,but lost their ability to produce proteins.Pseudogene was used to be considered as a typical kind of non-codingjunk DNA.Increasing investigations,however,have shown that pseudogenes play important roles in gene regulation and genome evolution.The progress of research on pseudogenes is summarized in light of the origin and sequence characteristics of pseudogenes,identification of pseudogenes,genomic distribution,behaviour of its molecular evolution and functioning.
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Sequence (biology)
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ABSTRACT A simple kinetic model is developed that describes the accumulation of processed pseudogenes in a functional gene family. Insertion of new pseudogenes occurs at rate ν per gene and is countered by spontaneous deletion (at rate δ per DNA segment) of segments containing processed pseudogenes. If there are k functional genes in a gene family, the equilibrium number of processed pseudogenes is k(ν/δ), and the percentage of functional genes in the gene family at equilibrium is 1/[1 + (ν/δ)]. ν/δ values estimated for five gene families ranged from 1.7 to 15. This fairly narrow range suggests that the rates of formation and deletion of processed pseudogenes may be positively correlated for these families. If δ is sufficiently large relative to the per nucleotide mutation rate μ (δ > 20μ), processed pseudogenes will show high homology with each other, even in the absence of gene conversion between pseudogenes. We argue that formation of processed pseudogenes may share common pathways with transposable elements and retroviruses, creating the potential for correlated responses in the evolution of processed pseudogenes due to direct selection for control of transposable elements and/or retroviruses. Finally, we discuss the nature of the selective forces that may act directly or indirectly to influence the evolution of processed pseudogenes.
Pseudogene
Molecular evolution
Gene conversion
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Abstract Pseudogenes are those regions in a genome that have sequence similarity to functional genes but have decayed and have no obvious functions. It is estimated that the human genome contains more than 10 000 easily recognisable pseudogenes and many more fragmented sequences, that arose mainly through one of the following three mechanisms: duplication, retrotranposition and spontaneous loss of function. The majority of the human retrotransposed (i.e. processed) pseudogenes are primate specific, arising from a burst of retrotransposition activities approximately 45 Ma. Although most of the human pseudogenes are most likely too degenerated to perform a biological function, ∼20% of them exhibit evidence of transcriptional activity based on data from multiple genomic studies. Furthermore, a handful of pseudogene transcripts have been demonstrated experimentally to gain novel functions as noncoding ribonucleic acids (RNAs) , indicating that pseudogenes could be a reservoir for evolution innovation. Key Concepts: Pseudogenes are prevalent in the human genome and other mammalian genomes. Most human pseudogenes are from past retrotranspositions occurring before the split of primate from other lineages. Pseudogenes are a good source of DNA sequences for studying genome evolution. Most human pseudogenes are most likely ‘dead’ but many of them can be transcribed. Some human pseudogenes have adopted functions as noncoding RNAs.
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