SEARCH · Search PubMed

Results for “pseudogene”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources

PubMed2001

Simulating pseudogene evolution in vitro: determining the true number of mutations in a lineage.

Hypermutagenic PCR has been used to simulate pseudogene evolution of the Escherichia coli R67 dihydrofolate reductase gene. Each time the most divergent clone was used as template for another round of hypermutagenesis. After six rounds, with an average mutation rate of 0.05 per base per round, up to a 46% nucleic acid sequence variation was achieved. For a few clones the protein information content could be annihilated. As the intermediates were cloned and sequenced, it was possible to establish the real lineage and compute the true number of mutations. Not surprisingly the true number of forward and back mutations as well as variable sites exceeded those based on comparing any single intermediate to the initial sequence. However, the true number of forward and backward mutations, as well as the number of variable sites, increased linearly with sequence divergence from the original sequence, suggesting an empirical means to correct for branch lengths.

Base Sequence↗

PubMed1987

Human immunoglobulin C lambda 6 gene encodes the Kern+Oz-lambda chain and C lambda 4 and C lambda 5 are pseudogenes.

Six nonallelic immunoglobulin lambda constant region genes have been previously characterized on a 40-kilobase stretch of DNA. The nucleotide sequences of the three upstream genes of this cluster (C lambda 1, C lambda 2, C lambda 3) have been determined by other workers and shown to encode, respectively, the isotypic Mcg, Kern-Oz-, and Kern-Oz+ constant region of the lambda chains. In this paper, we report the sequence of the three downstream genes of this cluster and show that two of them (C lambda 4 and C lambda 5) are pseudogenes. However, C lambda 6 encodes a Kern+Oz- chain and corresponds to the fourth isotype described among the lambda proteins sequenced so far. A potentially active J lambda (joining) segment, with the canonical heptamer and nonamer sequences for rearrangement, is located 1.5 kilobases upstream of C lambda 6. The amino acid sequence encoded by the C lambda 6 gene is compared with the constant region sequences of various monoclonal Bence Jones lambda proteins. Allotypic and isotypic differences confirm the polymorphism and complexity of the human C lambda locus.

Amino Acid Sequence↗

PubMed1988

Tandemly repeated tRNA pseudogenes in photobacterium.

A region distal to three tRNA genes in Photobacterium phosphoreum, a Gram-negative eubacterium, unexpectedly contains a high number of repeated DNA segments that are closely related to the adjacent tRNAPro gene. The 5' to 3' order of this cluster is tRNAPro-tRNAHis-tRNAPro followed by eight tRNAPro-like structures interspersed by rho-independent terminators. The two tRNAPro genes, which are identical, and the tRNAHis gene have 86% and 87% positional identity, respectively, to their counterparts in the argT operon of Escherichia coli. The facts that these tRNA-like structures are not transcribed, in contrast to the tRNA retropseudogenes of eukaryotes, and that these structures are clustered near their progenitor suggest they are an unusual class of tRNA pseudogenes that arose by tandem duplication.

Base Sequence↗

PubMed1988

Immunoglobulin heavy chain variable region gene evolution: structure and family relationships of two genes and a pseudogene in a teleost fish.

Nucleotide sequences for two immunoglobulin heavy chain variable region (VH) genes and one pseudogene in the goldfish (Carassius auratus) and the family relationships and distribution of these genes in individual fish are presented. Comparison of the nucleotide and inferred amino acid sequences of goldfish and other vertebrate VH genes indicates that goldfish VH genes show the major VH gene regulatory and structural features (5'-putative promoter region, split hydrophobic leader, three framework and two complementarity-determining regions, and 3'-recombination signals for VH to diversity region joining) and that goldfish VH genes are not more closely related to one another than they are to VH genes of evolutionarily distant vertebrates such as the mammals. Goldfish VH genes appear to exist in distinct families, and individual goldfish can carry from none to apparently greater than 15 genes of a given family. These results suggest that whereas the basic structure of VH genes has been conserved in evolution, there may be substantial variation in the nature and population distribution of VH gene families in the vertebrates.

Amino Acid Sequence↗

PubMed1989

Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes.

The expression of genes coding for variable surface glycoproteins (VSGs) in Trypanosoma equiperdum is linked to duplicative transpositions of silent, basic copy sequences into telomere-linked expression sites. Examination of three independently derived late-appearing trypanosome clones expressing VSG-78 revealed that the expressed gene in all cases is composed of sequences derived from three or four individual silent genes. The 182 base pairs at the 3' end of the coding sequence are derived from one silent gene, the 3' donor. The remaining 5' segment is a mosaic structure containing variable-length segments derived from two, or perhaps three, related silent genes. All of the silent genes that participate in the construction of the VSG-78 expression-linked copy (ELC) genes contain multiple stop codons and are unable to code for VSGs. Individual silent pseudogenes complement one another in the mosaic structure of the 5' portions of the ELC genes and create functional VSG genes. The joining of the 3' and 5' portions of the composite genes occurs in short regions of homology and suggests a mechanism by which the ordered expression of the VSG genes is generated.

Animals↗

PubMed1990

Selective amplification of an mRNA and related pseudogene for a human ADP-ribosylation factor, a guanine nucleotide-dependent protein activator of cholera toxin.

ADP-ribosylation factors (ARFs) are approximately 20-kDa proteins that act as GTP-dependent allosteric activators of cholera toxin. With deoxyinosine-containing degenerate oligonucleotide primers corresponding to conserved GTP-binding domains in ARFs, the polymerase chain reaction (PCR) was used to amplify simultaneously from human DNA portions of three ARF genes that include codons for 102 amino acids, with intervening sequences. Amplification products that differed in size because of differences in intron sizes were separated by agarose gel electrophoresis. One amplified DNA contained no introns and had a sequence different from those of known ARFs. Based on this sequence, selective oligonucleotide probes were prepared and used to isolate clone psi ARF 4, a putative ARF pseudogene, from a human genomic library in lambda phage EMBL3. Reverse transcription-PCR was then used to clone from human poly(A)+ RNA the cDNA corresponding to the expressed homolog of psi ARF 4, referred to as human ARF 4. It appears that psi ARF 4 arose during human evolution by integration of processed ARF 4 mRNA into the genome. Human ARF 4 differs from previously identified mammalian ARFs 1, 2, and 3. Hybridization of ARF 4-specific oligonucleotide probes with human, bovine, and rat RNA revealed a single 1.8-kilobase mRNA, which was clearly distinguished from the 1.9-kilobase mRNA for ARF 1 in these tissues. The PCR provides a powerful tool for investigating diversity in this and other multigene families, especially with primers targeted at domains believed to have functional significance.

ADP-Ribosylation Factors↗

PubMed1992

On "genomenclature": a comprehensive (and respectful) taxonomy for pseudogenes and other "junk DNA".

Genomic nomenclature has not kept pace with the levels and depth of analyzing and understanding genomic structure, function, and evolution. We wish to propose a general terminology that might aid the integrated study of evolution and molecular biology. Here we designate as a "nuon" any stretch of nucleic acid sequence that may be identifiable by any criterion. We show how such a general term will facilitate contemplation of the structural and functional contributions of such elements to the genome in its past, current, or future state. We focus in this paper on pseudogenes and dispersed repetitive elements, since their current names reflect the prevalent view that they constitute dispensable genomic noise (trash), rather than a vast repertoire of sequences with the capacity to shape an organism during evolution. This potential to contribute sequences for future use is reflected in the suggested terms "potonuons" or "potogenes." If such a potonuon has been coopted into a variant or novel function, an evolutionary process termed "exaptation," we employ the term "xaptonuon." If a potonuon remains without function (nonaptive nuon), it is a "nonaptation" and we term it "naptonuon." A number of examples for potonuons and xaptonuons are given.

Animals↗

PubMed1995

Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13.

Steroidogenic acute regulatory protein (StAR) appears to mediate the rapid increase in pregnenolone synthesis stimulated by tropic hormones. cDNAs encoding StAR were isolated from a human adrenal cortex library. Human StAR, coexpressed in COS-1 cells with cytochrome P450scc and adrenodoxin, increased pregnenolone synthesis > 4-fold. A major StAR transcript of 1.6 kb and less abundant transcripts of 4.4 and 7.5 kb were detected in ovary and testis. Kidney had a lower amount of the 1.6-kb message. StAR mRNA was not detected in other tissues including placenta. Treatment of granulosa cells with 8-bromo-adenosine 3',5'-cyclic monophosphate for 24 hr increased StAR mRNA 3-fold or more. The structural gene encoding StAR was mapped using somatic cell hybrid mapping panels to chromosome 8p. Fluorescence in situ hybridization placed the StAR locus in the region 8p11.2. A StAR pseudogene was mapped to chromosome 13. We conclude that StAR expression is restricted to tissues that carry out mitochondrial sterol oxidations subject to acute regulation by cAMP and that StAR mRNA levels are regulated by cAMP.

Animals↗

PubMed1995

Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene.

Low-copy repeats have been associated with genomic rearrangements and have been implicated in the generation of mutations in several diseases. Here we characterize a subset of low-copy repeats in the spinal muscular atrophy (SMA) region in human chromosome 5q13. We show that this repeated sequence, named c41-cad, is a highly expressed pseudogene derived from an intact neuronal cadherin gene, Br-cadherin, situated on 5p13-14. Br-cadherin is expressed specifically in the brain, whereas the c41-cad transcripts are 10-15 times more abundant and are present in all tissues examined. We speculate that the c41-cad repeats, separately or in concert with other repeats in the SMA region, are involved in the pathogenesis of SMA by promoting rearrangements and deletions.

Amino Acid Sequence↗

PubMed1997

Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes.

In an unprecedented finding, Davis et al. [Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N. & Parker, W. D., Jr. (1997) Proc. Natl. Acad. Sci. USA 94, 4526-4531] used an unusual DNA isolation method to show that healthy adults harbor a specific population of mutated mitochondrial cytochrome c oxidase (COX) genes that coexist with normal mtDNAs. They reported that this heteroplasmic population was present at a level of 10-15% in the blood of normal individuals and at a significantly higher level (20-30%) in patients with sporadic Alzheimer's disease. We provide compelling evidence that the DNA isolation method employed resulted in the coamplification of authentic mtDNA-encoded COX genes together with highly similar COX-like sequences embedded in nuclear DNA ("mtDNA pseudogenes"). We conclude that the observed heteroplasmy is an artifact.

Adult↗

PubMed1999

Mouse trp2, the homologue of the human trpc2 pseudogene, encodes mTrp2, a store depletion-activated capacitative Ca2+ entry channel.

Capacitative Ca2+ entry (CCE) is Ca2+ entering after stimulation of inositol 1,4,5-trisphosphate (IP3) formation and initiation of Ca2+ store depletion. One hallmark of CCE is that it can also be triggered merely by store depletion, as occurs after inhibition of internal Ca2+ pumps with thapsigargin. Evidence has accumulated in support of a role of transient receptor potential (Trp) proteins as structural subunits of a class of Ca2+-permeable cation channels activated by agonists that stimulate IP3 formation-very likely through a direct interaction between the IP3 receptor and a Trp subunit of the Ca2+ entry channel. The role of Trp's in Ca2+ entry triggered by store depletion alone is less clear. Only a few of the cloned Trp's appear to enhance this type of Ca2+ entry, and when they do, the effect requires special conditions to be observed, which native CCE does not. Here we report the full-length cDNA of mouse trp2, the homologue of the human trp2 pseudogene. Mouse Trp2 is shown to be readily activated not only after stimulation with an agonist but also by store depletion in the absence of an agonist. In contrast to other Trp proteins, Trp2-mediated Ca2+ entry activated by store depletion is seen under the same conditions that reveal endogenous store depletion-activated Ca2+ entry, i.e., classical CCE. The findings support the general hypothesis that Trp proteins are subunits of store- and receptor-operated Ca2+ channels.

Amino Acid Sequence↗

PubMed1997

Molecular genetic analysis of a human neuropeptide Y receptor. The human homolog of the murine "Y5" receptor may be a pseudogene.

Neuropeptide Y is a 36-amino-acid peptide amide with numerous biological activities. These functions are mediated through several pharmacologically distinct receptors. To date five receptor subtypes have been cloned. Here we report the isolation, by low stringency homology cloning from a hypothalamic library, of a cDNA encoding the human homolog of the murine neuropeptide Y receptor subsequently reported (). Translation of the human Y1-like receptor clone suggested that it encoded a receptor which is truncated in the third extracellular loop. Comparison of the human Y1-like sequence to that of the human Y1 receptor suggested that the truncated receptor could have resulted from a frameshift due to a single nucleotide deletion in the sixth transmembrane domain. Southern blot analysis suggested that the gene is single copy in the human genome. The gene is located on chromosome 5q. To test the hypothesis that allelic variation of nucleic acid length within the sixth transmembrane domain of the Y1-like receptor may exist to produce a functional receptor, genomic DNA from 192 individuals of various ages, ethnic backgrounds, and degrees of obesity were analyzed electrophoretically and by direct sequencing. No variation was detected in any of the subjects, indicating that this receptor subtype may be a transcribed pseudogene in humans.

Amino Acid Sequence↗

PubMed1999

The mouse p97 (CDC48) gene. Genomic structure, definition of transcriptional regulatory sequences, gene expression, and characterization of a pseudogene.

Here we present the first description of the genomic organization, transcriptional regulatory sequences, and adult and embryonic gene expression for the mouse p97(CDC48) AAA ATPase. Clones representing two distinct p97 genes were isolated in a genomic library screen, one of them likely representing a non-functional processed pseudogene. The coding region of the gene encoding the functional mRNA is interrupted by 16 introns and encompasses 20.4 kilobase pairs. Definition of the transcriptional initiation site and sequence analysis showed that the gene contains a TATA-less, GC-rich promoter region with an initiator element spanning the transcription start site. Cis-acting elements necessary for basal transcription activity reside within 410 base pairs of the flanking region as determined by transient transfection assays. In immunohistological analyses, p97 was widely expressed in embryos and adults, but protein levels were tightly controlled in a cell type- and cell differentiation-dependent manner. A remarkable heterogeneity in p97 immunostaining was found on a cellular level within a given tissue, and protein amounts in the cytoplasm and nucleus varied widely, suggesting a highly regulated and intermittent function for p97. This study provides the basis for a detailed analysis of the complex regulation of p97 and the reagents required for assessing its functional significance using targeted gene manipulation in the mouse.

Adenosine Triphosphatases↗

PubMed2004

A frameshift mutation and alternate splicing in human brain generate a functional form of the pseudogene cytochrome P4502D7 that demethylates codeine to morphine.

A frameshift mutation 138delT generates an open reading frame in the pseudogene, cytochrome P4502D7 (CYP2D7), and an alternate spliced functional transcript of CYP2D7 containing partial inclusion of intron 6 was identified in human brain but not in liver or kidney from the same individual. mRNA and protein of the brain variant CYP2D7 were detected in 6 of 12 human autopsy brains. Genotyping revealed the presence of the frameshift mutation 138delT only in those human subjects who expressed the brain variant CYP2D7. Genomic DNA analysis in normal volunteers revealed the presence of functional CYP2D7 in 4 of 8 individuals. In liver, the major organ involved in drug metabolism, a minor metabolic pathway mediated by CYP2D6 metabolizes codeine (pro-drug) to morphine (active drug), whereas norcodeine is the major metabolite. In contrast, when expressed in Neuro2a cells, brain variant CYP2D7 metabolized codeine to morphine with greater efficiency compared with the corresponding activity in cells expressing CYP2D6. Morphine binds to micro-opioid receptors in certain regions of the central nervous system, such as periaqueductal gray, and produces pain relief. The brain variant CYP2D7 and micro-opioid receptor colocalize in neurons of the periaqueductal gray area in human brain, indicating that metabolism of codeine to morphine could occur at the site of opioid action. Histio-specific isoforms of P450 generated by alternate splicing, which mediate selective metabolism of pro-drugs within tissues, particularly the brain, to generate active drugs may play an important role in drug action and provide newer insights into the genetics of metabolism.

Alternative Splicing↗

PubMed1995

Constitutive human steroid 21-hydroxylase promoter gene and pseudogene activity in steroidogenic and nonsteroidogenic cells with the luciferase gene as a reporter.

This study was directed toward initial comparison and characterization of the activities of the human steroid 21-hydroxylase gene (CYP21) and pseudogene (CYP21P) promoters. DNA fragments containing the promoter regions of CYP21 and CYP21P were amplified and cloned into promoterless luciferase reporter plasmids either containing or lacking an enhancer element. Cells of the nonsteroidogenic COS-1 cell line, and the steroidogenic Y-1 cell line were transiently transfected with these recombinant plasmids and a beta-galactosidase cotransfection control plasmid. Cellular lysates were analyzed for luciferase and beta-galactosidase activities. In the nonsteroidogenic system, transfectants with either the CYP21 or CYP21P upstream sequence in enhancer containing plasmids showed a 2.3 fold increase (p < .001) in light production over controls. In the steroidogenic Y-1 cell system, these same CYp21 and CYP21P transfectants showed a 14.3 (+/- 0.8) and 5.2 (+/- 0.6) fold increase in luciferase activity respectively (p < .001) Transfections with recombinant reporter plasmids lacking an enhancer produced light emission which was not significantly different than controls. These observations indicate that 1.) one or more of the 35 nucleotide differences between the CYP21 and CYP21P upstream regions alters a DNA recognition site important for transcriptional activation of this gene in steroidogenic cells, 2.) the steroidogenic milieu has a stimulatory effect on both CYP21 and CYP21P promoter activities, and 3.) based on the minimal promoter activity observed in either cell type transfected with constructs lacking an enhancer element, both of these promoter sequences are enhancer dependent under constitutive conditions in both steroidogenic and nonsteroidogenic cells.

Adrenal Hyperplasia, Congenital↗

PubMed2018

Long non-coding RNA metallothionein 1 pseudogene 3 promotes p2y12 expression by sponging miR-126 to activate platelet in diabetic animal model.

Platelet hyperaggregation and hypercoagulation are associated with increase of thrombogenic risk, especially in patients with type 2 diabetes (T2D). High activity of P2Y12 receptor is found in T2D patients, exposing such patients to a prothrombotic condition. P2Y12 is a promising target for antiplatelet, but due to P2Y12 receptor constitutive activation, the clinical practical phenomena such as "clopidogrel resistance" are commonly occurring. In this study, we investigate the role of lncRNA on platelet activation. By lncRNA array, we screened thousands of differentially expressed lncRNA in megakaryocytes from T2D patients and confirmed that lncRNA metallothionein 1 pseudogene 3 (MT1P3) was significantly upregulated in megakaryocytes from T2D patients than in healthy controls. And we further investigate the biofunction of MT1P3 on platelet activation and the regulatory mechanism on p2y12. MT1P3 was positively correlated with p2y12 mRNA levels and promoted p2y12 expression by sponging miR-126. Knockdown of MT1P3 by siRNA reduced p2y12 expression, inhibiting platelet activation and aggregation in diabetes animal model. In conclusion, our findings identify MT1P3 as a key regulator in platelet activation by increasing p2y12 expression through sponging miR-126 under T2D condition. These findings may provide a new insight for managing platelet hyperactivity-related diseases.

Animals↗

PubMed2002

Determination of haploid DNA sequences in humans: application to the glucocerebrosidase pseudogene.

Variation analyses in the human genome at the sequence level, especially human genetic population analysis and genetic epidemiology, are hampered by the difficulty to ascertain haplotypes on autosomal regions. We have designed a new methodological approach to obtain autosomal haploid sequences from diploid organisms. First, genotypes are unambiguously determined through long-range PCR and diploid DNA sequencing. Second, cloning the whole PCR-amplified segment and sequencing a single clone for those fragments that presented a heterozygous position discern the allelic phase. The second allele is deduced from the genotype, and the phase reconfirmed by sequencing a second clone. A hundred human chromosomes were analysed for a 5.4 kb encompassing the glucocerebrosidase pseudogene on human chromosome 1. Haplotypes were unambiguously ascertained for all samples. The manner to combine the used techniques makes this approach a novelty. Haploid sequences from diploid organisms are obtained in a less time consuming and more accurate manner than in other used procedures.

Glucosylceramidase↗

PubMed1990

Null alleles of human complement C4. Evidence for pseudogenes at the C4A locus and for gene conversion at the C4B locus.

The two genes for the C4A and C4B isotypes of the fourth component of human complement are located in the MHC class III region. Previous studies have demonstrated the unusual expression of C4 genes in the form of aberrant or duplicated haplotypes. Null alleles of C4A or C4B (AQ0 or BQ0) have been defined by the absence of gene products and occur at frequencies of 0.1-0.3. However, only some C4 null alleles are due to gene deletions, the remainder were thought to be nonexpressed genes. We have analyzed the C4 gene structure of 26 individuals lacking either C4A or C4B protein. The DNA of individuals with apparently nonexpressed C4 genes was tested for the presence of C4A- and C4B-specific sequences using restriction fragment analysis and isotype-specific oligonucleotide hybridization of DNA amplified by polymerase chain reaction. All nondeleted AQ0 allels had C4A-specific sequences and may thus be described as pseudogenes, whereas the nondeleted BQ0 alleles had C4A-instead of C4B-specific sequences. Gene conversion is the probable mechanism by which a C4A gene is found at the second C4 locus normally occupied by C4B genes.

Alleles↗