Search PubMed⌕ Search

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.

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

At least 109 records · Page 6Linked to original sources
PubMed1992

Nucleotide sequence of a mouse Tcp-1 pseudogene: a nucleotide record for a t complex gene carried by an ancestor of the mouse.

We have isolated clones of a processed pseudogene of mouse t complex polypeptide 1 (Tcp-1) and determined the nucleotide sequence of the pseudogene. The pseudogene was 1363 bp long and had no intron. The Tcp-1 pseudogene had 88.4% or 88.3% nucleotide identity to the mouse Tcp-1 cDNA of wild-type (Tcp-1b) or t haplotype (Tcp-1a), and 87.5% identity to the rat Tcp-1 cDNA. On 12 nucleotide positions where the open reading frames (ORFs) of mouse Tcp-1b and Tcp-1a cDNAs have bp substitutions, the Tcp-1 pseudogene had 6 bp identical to Tcp-1b, 5 bp identical to Tcp-1a and 1 bp not identical to neither. On ten amino acid positions where TCP-1B and TCP-1A polypeptides have substitutions, deduced amino acids of the Tcp-1 pseudogene had four amino acids identical to TCP-1B, five amino acids identical to TCP-1A and one amino acid identical to neither. These results suggest that the ancestral mouse Tcp-1 gene would have had no significant difference between the resemblance to Tcp-1b and that to Tcp-1a before they were diverged and that amino acids of TCP-1B and TCP-1A would have been substituted in similar high rates.

Amino Acid Sequence↗
PubMed1993

Concerted evolution in the GAPDH family of retrotransposed pseudogenes.

In murine rodents the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) multigene family includes more than 300 retroprocessed pseudogenes. Its single functional gene encodes GAPDH, an enzyme of glycolysis. Because of its manageable size, this family is a good model for the study of genome cohesion and evolution. By sequence comparison of several GAPDH pseudogenes in Rattus norvegicus and Mus musculus, we have obtained evidence that (i) the GAPDH family still generates new pseudogenes; we note in each species the beginning of a process of species-specific evolution since the pseudogenes of one genus on average cluster more with one another than they do with those of the other genus, and (ii) the GAPDH family contains diversified subfamilies. These findings suggest a certain level of transcription and transposition of the pseudogenes independent of the functional gene which may result from various mechanisms. The homogenization we observe may be due to the pseudogenes themselves (concerted evolution in a strict sense), which explains the occurrence of long-term homogenization of old sequences and subfamily groupings.

Animals↗
PubMed1989

Human glyceraldehyde-3-phosphate dehydrogenase pseudogenes: molecular evolution and a possible mechanism for amplification.

We screened two human genomic libraries and isolated 14 different clones, designated lambda G1 and EG1-EG13, homologous to human glyceraldehyde-3-phosphate dehydrogenase (GAPD) cDNA. Subcloning and sequencing these recombinant phages led us to classify them as five different pseudogenes (psi G1-psi G5). All these sequences show such features typical of processed pseudogenes as numerous mutations, insertions, and deletions. The identity of numerous mutated sites among these pseudogenes and the presence of two Alu sequences flanking both ends of psi G1 suggest that GAPD pseudogenes originated from a unique reverse transcribed mRNA followed by gene duplication. The rate of nucleotide substitutions per site per year for known GAPD functional genes is low both for the synonymous substitutions (1.87 x 10(-9] and for the nonsynonymous substitutions (0.12 x 10(-9] and indicates that the GAPD cDNA sequence is well conserved not only at the amino acid level, but also at the nucleotide level. The rate of nucleotide substitutions per site per year for GAPD pseudogenes shows a higher value (5.9 x 10(-9] and suggests that these pseudogenes do not have any functional role.

Base Sequence↗
PubMed1993

Silk moth chorion pseudogenes: hallmarks of genomic evolution by sequence duplication and gene conversion.

The part of the genetic locus of the domesticated silk moth, Bombyx mori, in which high cysteine (Hc) chorion genes of late developmental specificity reside contains regions encompassing gene-like sequences which exhibit properties distinct from those of functional Hc genes. One of these regions has been characterized and shown to contain a chorion pseudogene, psi HcB.15, which shares pronounced similarities with a transcribed chorion pseudogene, psi HcB.12/13, which was characterized previously. Both pseudogenes are homologous to HcB chorion genes but bear multiple single nucleotide substitutions and short segmental mutations (insertions and deletions) which introduce translational frame shifts and termination codons in the coding regions. Structural characteristics unique to the two pseudogenes suggest that psi HcB.15 was generated first from a functional HcB gene and gave rise subsequently to psi HcB 12/13 as a result of a sequence duplication event. The two pseudogenes can be distinguished from each other by the presence of distinct regions of similarity to the consensus sequence of functional HcB genes which appear to have arisen from gene-conversion-mediated correctional events. These findings lend support to the hypothesis that chorion pseudogene sequences represent reservoirs of genetic information that participates in the evolution of the chorion locus rather than relics of inactivated genes passively awaiting extinction.

Animals↗
PubMed2002

Multiple nuclear pseudogenes of mitochondrial DNA exist in the canine genome.

Many copies of nuclear counterparts of mitochondrial DNA (mtDNA) were found in nuclear DNA from sperm heads of the domestic dog, Canis familiaris, by DNA-DNA hybridization and DNA sequencing. Nuclear counterparts homologous to the mtDNA D-loop region were cloned into lambda phage vectors (EMBL4 and lambda gt11), and nucleotide sequences of seven different mtDNA pseudogenes were then determined. The seven pseudogenes were E3 (474 bp; 82% homology with canine mtDNA), E13 (1867 bp; 67%), 8B (2375 bp; 78%), 12A (2650 bp; 79%), 33 (4131 bp; 86%), 47 (4251 bp; 86%), and E17 (5721 bp; 71%). These seven mtDNA pseudogenes corresponded to portions of cytoplasmic mtDNA containing the genes ile, ND1, leu, 16S rRNA, val, 12S rRNA, phe, D-loop, pro, thr, cytb, and glu. A neighbor-joining phylogenetic tree constructed from 12S rRNA sequences in mtDNA pseudogenes 8B, 33, 47, and E17 and in 10 mtDNA fragments from other species showed that these four pseudogenes form a monophyletic clade with canine mtDNA. A neighbor-joining phylogenetic tree based on the 318-bp cytb region showed that the canine pseudogenes existed before the divergence of 17 related canids, and their divergence dates were calculated at around 4.4 to 8.6 million years ago.

Animals↗
PubMed2000

Characterization of a partial pseudogene homologous to the Hermansky-Pudlak syndrome gene HPS-1; relevance for mutation detection.

The HPS-1 gene is the first gene found to be responsible for the autosomal recessive disorder Hermansky-Pudlak syndrome (HPS). HPS is characterized by oculocutaneous albinism, a platelet storage pool deficiency, and ceroid lipofuscinosis. The HPS-1 gene has been mapped to chromosome 10q23.1-23.3 and encodes a 79-kDa protein of unknown function with no homology to any known protein. A sequence database search has revealed that a portion of clone HS 1119A7 shows high sequence similarity to HPS-1 cDNA. By performing sequence alignments and PCR amplification of cDNA from several human tissues, we have shown that part of this clone consists of an unprocessed partial HPS-1 pseudogene located on chromosome 22q12.2-12.3. The pseudogene contains several intact HPS-1 exons and shows 95% sequence homology to the HPS-1 cDNA. Exon 6 of the pseudogene has 100% sequence homology to exon 6 of HPS-1 itself. In the pseudogene, this exon is surrounded by portions of both its normal flanking introns. These data provide the first characterization of an HPS-1 pseudogene, called HPS1-psi1. During amplification of exon 6 of the HPS-1 gDNA for mutation identification, the pseudogene might also be amplified, leading to a false positive for mutation. In addition, amplification of specific parts of the HPS-1 cDNA (e.g., exons 2-5) for mutation detection might lead to false positives for mutations, if the cDNA is contaminated with gDNA. This calls for caution when employing these screening approaches.

Albinism, Oculocutaneous↗
PubMed2001

A genome-wide survey of human thioredoxin and glutaredoxin family pseudogenes.

The thioredoxin/glutaredoxin family consists of small heat-stable proteins that have a highly conserved CXXC active site and that participate in the regulation of many redox reactions. We have searched the human genome sequence to find putative pseudogenes (non-functional copies of protein-coding genes) for all known members of this family. This survey has resulted in the identification of seven processed pseudogenes for human Trx1 and two more for human Grx1. No evidence for the presence of processed pseudogenes has been found for the remaining members of this family. In addition, we have been unable to detect any non-processed pseudogenes derived from any member of the family in the human genome. The seven thioredoxin pseudogenes can be divided into two groups: Trx1-psi2, -psi3, -psi4, -psi5 and -psi6 arose from the functional ancestor, whereas Trx1-psi1 and -psi7 originated from Trx1-psi2 and -psi6, respectively. In all cases, the pseudogenes originated after the human/rodent radiation as shown by phylogenetic analysis. This is also the case for Grx1-psi1 and Grx1-psi2, which are placed between rodent and human sequences in the phylogenetic tree. Our study provides a molecular record of the recent evolution of these two genes in the hominid lineage.

Animals↗
PubMed1988

Mouse cytoskeletal gamma-actin: analysis and implications of the structure of cloned cDNA and processed pseudogenes.

The nucleotide sequence corresponding to almost the whole of a mouse gamma-cytoskeletal actin mRNA was determined from overlapping cloned DNA copies derived from brain mRNA. Several gamma-actin processed pseudogenes were isolated from a library of cloned DBA mouse genomic DNA, and the nucleotide sequences of these were determined and compared with that of the cDNA. This showed that two of these pseudogenes had arisen from a gene duplication or amplification event, and indicated that they had subsequently undergone partial correction against one another. The relative ages of the pseudogenes were estimated on the basis of their percentage divergence from the cDNA sequence and these were compared with an estimation based on the number of presumed silent mutations in the cDNA since each pseudogene had arisen. Consistent results were obtained, except in the case of one pseudogene which also showed an anomalous regional distribution of differences from the cDNA sequence. One way of accounting for the features of this anomalous pseudogene is by postulating that it is derived from a second functional gene for gamma-actin, different from that represented by the cDNA described here.

Actins↗
PubMed1992

A human aldehyde dehydrogenase (aldose reductase) pseudogene: nucleotide sequence analysis and assignment to chromosome 3.

Four cosmid clones containing putative pseudogenes for human aldehyde dehydrogenase (Aldose reductase) were isolated from libraries made to two individuals. These clones show different patterns on digestion with restriction endonucleases and probably represent distinct and separate loci. The DNA sequence of one of the putative pseudogenes (cosmid AR.F) was determined, and comparisons demonstrate 89.7% homology with the cDNA sequence of the functional aldose reductase gene. This pseudogene sequence contains no intronic sequences, whereas the functional aldose reductase has nine introns. In addition, the homology disappears in region 5' to the transcription start site for the cDNA, implying that regulatory elements such as the promoter are missing from this pseudogene. The pseudogene defined by cosmid AR.F has been mapped to chromosome 3 by polymerase chain reaction using amplimers specific for this pseudogene to amplify DNA from somatic cell hybrids.

Aldehyde Reductase↗
PubMed2004

Isolation and characterization of Rac1 pseudogenes (psi1Rac1-psi4Rac1) in the human genome.

Ras-related C3 toxin substrate 1 (Rac1) is a small Rho-GTPase with important functions in fundamental cellular processes such as cytoskeleton rearrangements, signal transduction, cell cycle progression and malignant transformation. Using Rac1 primer, we identified a 5.5-kb DNA sequence on chromosome 4 (Chr. 4) in the human genome, containing the intronless protein coding sequence of Rac1. Sequence analysis revealed features of a processed pseudogene, which we named psi1Rac1, that could be detected by Southern blot and polymerase chain reaction (PCR) on genomic DNA. A psi1Rac1 pseudogene transcript was not detected by reverse transcription-polymerase chain reaction (RT-PCR), nor had the psi1Rac1 promoter any transcriptional activity. In addition, three other intronless pseudogenes of Rac1 on chromosomes 4, 13 and X were identified (psi1Rac1-psi4Rac1) sharing an 86-96% sequence similarity with Rac1. Neither RT-PCR with pseudogene specific restriction enzymes, nor the sequencing of 130 cDNA clones from benign and malignant breast tissue and cell lines, detected the transcription of any of the Rac1 pseudogenes (psi2Rac1-psi4Rac1). Existence of Rac1 pseudogenes should be taken into consideration when analyzing genomic alterations of the human Rac1 gene.

Amino Acid Sequence↗
PubMed2005

Reliability of mitochondrial DNA in an acanthocephalan: the problem of pseudogenes.

The utility of mitochondrial DNA as a molecular marker for evolutionary studies is well recognized. However, several problems can arise when using mitochondrial DNA, one of which is the presence of nuclear mitochondrial pseudogenes, or Numts. Pseudogenes of cytochrome oxidase I were preferentially amplified from Acanthocephalus lucii (Acanthocephala) using a universal PCR approach. To verify the presence and abundance of pseudogenes, length heterogeneity analysis of the PCR fragments was performed. PCR products obtained with universal primers often contained fragments of different sizes. Cloned sequences from universal PCR products nearly always contained sequence abnormalities such as indels and/or stop codons. Based on these sequences, new primers were developed to specifically target mitochondrial DNA. Sequences obtained with these specific primers lacked abnormalities. Phylogenetic analysis produced a single most parsimonious tree in which pseudogenes obtained with universal primers grouped together as did putative mitochondrial DNA sequences obtained with specific primers. The pattern of codon bias observed in the pseudogenes suggests a single nuclear integration event from the mitochondria. This is the first reported occurrence of pseudogenes in an acanthocephalan, and it demonstrates the potential dangers associated with the use of universal primers.

Acanthocephala↗
PubMed2003

Characterization of angiosperm nrDNA polymorphism, paralogy, and pseudogenes.

Many early reports of ITS region (ITS 1, 5.8S, and ITS 2) variation in flowering plants indicated that nrDNA arrays within individuals are homogeneous. However, both older and more recent studies have found intra-individual nrDNA polymorphism across a range of plant taxa including presumed non-hybrid diploids. In addition, polymorphic individuals often contain potentially non-functional nrDNA copies (pseudogenes). These findings suggest that complete concerted evolution should not be assumed when embarking on phylogenetic studies using nrDNA sequences. Here we (1). discuss paralogy in relation to species tree reconstruction and conclude that a priori determinations of orthology and paralogy of nrDNA sequences should not be made based on the functionality or lack of functionality of those sequences; (2). discuss why systematists might be particularly interested in identifying and including pseudogene sequences as a test of gene tree sampling; (3). examine the various definitions and characterizations of nrDNA pseudogenes as well as the relative merits and limitations of a subset of pseudogene detection methods and conclude that nucleotide substitution patterns are particularly appropriate for the identification of putative nrDNA pseudogenes; and (4). present and discuss the advantages of a tree-based approach to identifying pseudogenes based on comparisons of sequence substitution patterns from putatively conserved (e.g., 5.8S) and less constrained (e.g., ITS 1 and ITS 2) regions. Application of this approach, through a method employing bootstrap hypothesis testing, and the issues discussed in the paper are illustrated through reanalysis of two previously published matrices. Given the apparent robustness of the test developed and the ease of carrying out percentile bootstrap hypothesis tests, we urge researchers to employ this statistical tool. While our discussion and examples concern the literature on plant systematics, the issues addressed are relevant to studies of nrDNA and other multicopy genes in other taxa.

DNA, Ribosomal↗
PubMed1991

Transcription of a human dopamine D5 pseudogene.

We have previously reported that the human genome contains the two pseudogenes psi DRD5-1, and psi DRD5-2, and that each share 94% homology when compared with the functional gene DRD5. There is only 2% difference at the nucleotide level between the two pseudogenes. We questioned whether these pseudogenes were transcribed, since transcription of either of these pseudogenes could result in false interpretation of in-situ hybridization and Northern blot analysis, using the DRD5 as a probe. We now report that we have detected transcription of one of the pseudogenes, psi DRD5-1, in several human brain areas, and this mRNA transcript is capable of producing a protein of 154 amino acids. Furthermore we report that PCR amplification of DRD5 or the pseudogenes in human tissue can result in the formation of chimer artifacts due to the co-amplification of three very similar genes.

Animals↗
PubMed1997

Patterns and rates of indel evolution in processed pseudogenes from humans and murids.

Patterns and rates of indel (deletions and insertions) evolution were characterized in 156 independently derived processed pseudogenes from humans and murids (mice and rats). A total of 441 deletions and 161 insertions were unambiguously identified. On a subset of 109 pseudogenes, we verified and confirmed the assumption that indels occur almost exclusively in the pseudogene and, therefore, in comparisons between pseudogenes and their functional paralogs, it is possible to assign polarity to the indel event. By comparing the characteristics of terminal truncations with those of internal deletions, we find support for the hypothesis that truncations are generated through a different pathway than internal deletions. The number of deletions and insertions per pseudogene was found to increase monotonically with time. Deletions occur on average once every 40 nucleotide substitutions, whereas insertions are much rarer, occurring once every 100 substitutions, indicating that the mechanisms involved in deletion formation are most probably different from those responsible for the formation of insertions. The age of the pseudogene, however, explained only 20 and 13%, respectively, of the variation in the number of deletions and insertions per site, indicating that factors other than evolutionary time may play a significant role in the evolutionary dynamics of indel accumulation. Since the rate of substitution has been previously shown to be higher in murids than in humans, we deduce that deletions and insertions accumulate proportionally faster in murids than in humans. Deletions and insertions in murid and human genomes do not contribute significantly to genome size.

Animals↗
PubMed2003

An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene.

A pseudogene is a gene copy that does not produce a functional, full-length protein. The human genome is estimated to contain up to 20,000 pseudogenes. Although much effort has been devoted to understanding the function of pseudogenes, their biological roles remain largely unknown. Here we report the role of an expressed pseudogene-regulation of messenger-RNA stability-in a transgene-insertion mouse mutant exhibiting polycystic kidneys and bone deformity. The transgene was integrated into the vicinity of the expressing pseudogene of Makorin1, called Makorin1-p1. This insertion reduced transcription of Makorin1-p1, resulting in destabilization of Makorin1 mRNA in trans by way of a cis-acting RNA decay element within the 5' region of Makorin1 that is homologous between Makorin1 and Makorin1-p1. Either Makorin1 or Makorin1-p1 transgenes could rescue these phenotypes. Our findings demonstrate a specific regulatory role of an expressed pseudogene, and point to the functional significance of non-coding RNAs.

Alleles↗
PubMed1999

Nuclear pseudogenes of mitochondrial DNA as a variable part of the human genome.

Novel pseudogenes homologous to the mitochondrial (mt) 16S rRNA gene were detected via different approaches. Eight pseudogenes were sequenced. Copy number polymorphism of the mtDNA pseudogenes was observed among randomly chosen individuals, and even among siblings. A mtDNA pseudogene in the Y-chromosome was observed in a YAC clone carrying only repetitive sequence tag site (STS). PCR screening of human yeast artificial chromosome (YAC) libraries showed that there were at least 5.7 x 10(5) bp of the mtDNA pseudogenes in each haploid nuclear genome. Possible involvement of the mtDNA pseudogenes in the variable part of the human nuclear genome is discussed.

Adolescent↗
PubMed1999

Transcriptional analysis of the PTEN/MMAC1 pseudogene, psiPTEN.

PTEN/MMAC1 is a recently characterized tumor suppressor. A pseudogene derived from the human PTEN/MMAC1 phosphatase, psiPTEN, has been reported. Recent analysis of the pseudogene revealed conflicting results about the expression of psiPTEN. In this study, we show that the PTEN/MMAC1 pseudogene is actively transcribed in all cells and tissues examined. In some cases, pseudogene transcripts were found to represent as much as 70% of the total PTEN/MMAC1 RNA. As psiPTEN is transcribed, there is a potential for misinterpretation of PTEN/MMAC1 mutations when RT-PCR techniques are used, as well as potential for a psiPTEN-encoded translation product. Although we were unable to detect a pseudogene protein product in the cell lines examined, a baculovirus produced GST pseudogene fusion protein exhibited phosphatase activity comparable to wild type. The results of this study, taken together, indicate the potential complication of PTEN/MMAC1 molecular analysis caused by the expression of psiPTEN.

Amino Acid Sequence↗
PubMed1988

The human somatic cytochrome c gene: two classes of processed pseudogenes demarcate a period of rapid molecular evolution.

We have isolated and determined the DNA sequences of the human somatic cytochrome c gene (HCS) and 11 processed pseudogenes. HCS is the functional homologue to the previously characterized rat somatic gene because it correctly encodes the human heart protein, is present in single copy in the human genome, is nearly identical in both size and intron/exon structure to rodent somatic genes, and shares a high degree of sequence homology with its rat counterpart including a well-conserved promoter region (77% over 250 nucleotides). In contrast to the rodent system, however, where the known pseudogenes all originated from a locus encoding the present day cytochrome c, the human pseudogenes are of two types. A predominant class of older pseudogenes came from a progenitor of HCS that encoded an ancestral form of the protein, while a second group of only a few young pseudogenes originated from a recent parent of HCS that encoded the current cytochrome c polypeptide. These two distinct classes of human pseudogenes provide a molecular record of the history of cytochrome c evolution in primates and demarcate a short period of rapid evolution of the functional gene.

Animals↗