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 1,513 records · Page 84Linked to original sources
PubMed1998

Simultaneous detection of five mutations in the steroid 21-hydroxylase gene using nested allele-specific amplification.

Congenital adrenal hyperplasia due to deficiency of steroid 21-hydroxylase (CYP21) is most frequently due to mutations that arise from the nearby CYP21 pseudogene. The mechanism involves either unequal crossing over, which deletes part of the CYP21 functional gene, or gene conversion which puts a mutation from the pseudogene into the functional gene. We have devised an assay to rapidly screen for five known mutations that are due to gene conversion within an 1,800 bp region of the CYP21 gene--I172N, V281L, Q318X, R356W, and a cluster of mutations in exon 6 (I236N, V237E, M239K). This method is based on a set of nested allele-specific polymerase chain reactions done simultaneously in one tube, for which we suggest the acronym NASA, for nested allele-specific amplification. The assay is capable of detecting the mutations individually as well as all combinations of mutations tested.

Adrenal Hyperplasia, Congenital↗
PubMed2001

Updating the str and srj (stl) families of chemoreceptors in Caenorhabditis nematodes reveals frequent gene movement within and between chromosomes.

The seven transmembrane receptor (str) and srj (renamed from stl) families of chemoreceptors have been updated and the genes formally named following completion of the Caenorhabditis elegans genome sequencing project. Analysis of gene locations revealed that 84% of the 320 genes and pseudogenes in these two families reside on the large chromosome V. Movements to other chromosomes, especially chromosome IV, have nevertheless been relatively common, but only one has led to further gene family diversification. Comparisons with homologs in C. briggsae indicated that 22.5% of these genes have been newly formed by gene duplication since the species split, while also showing that four have been lost by large deletions. These patterns of gene evolution are similar to those revealed by analysis of the equally large srh family of chemoreceptors, and are likely to reflect general features of nematode genome dynamics. Thus large random deletions presumably balance the rapid proliferation of genes and their degeneration into pseudogenes, while gene movement within and between chromosomes keeps these nematode genomes in flux.

Animals↗
PubMed2004

Complete genome sequence of Yersinia pestis strain 91001, an isolate avirulent to humans.

Genomics provides an unprecedented opportunity to probe in minute detail into the genomes of the world's most deadly pathogenic bacteria- Yersinia pestis. Here we report the complete genome sequence of Y. pestis strain 91001, a human-avirulent strain isolated from the rodent Brandt's vole-Microtus brandti. The genome of strain 91001 consists of one chromosome and four plasmids (pPCP1, pCD1, pMT1 and pCRY). The 9609-bp pPCP1 plasmid of strain 91001 is almost identical to the counterparts from reference strains (CO92 and KIM). There are 98 genes in the 70,159-bp range of plasmid pCD1. The 106,642-bp plasmid pMT1 has slightly different architecture compared with the reference ones. pCRY is a novel plasmid discovered in this work. It is 21,742 bp long and harbors a cryptic type IV secretory system. The chromosome of 91001 is 4,595,065 bp in length. Among the 4037 predicted genes, 141 are possible pseudo-genes. Due to the rearrangements mediated by insertion elements, the structure of the 91001 chromosome shows dramatic differences compared with CO92 and KIM. Based on the analysis of plasmids and chromosome architectures, pseudogene distribution, nitrate reduction negative mechanism and gene comparison, we conclude that strain 91001 and other strains isolated from M. brandti might have evolved from ancestral Y. pestis in a different lineage. The large genome fragment deletions in the 91001 chromosome and some pseudogenes may contribute to its unique nonpathogenicity to humans and host-specificity.

Carbohydrate Metabolism↗
PubMed2005

Characterization of the structure and expression of mouse Itpa gene and its related sequences in the mouse genome.

In the mouse genome, we found one processed Itpa gene-like sequence and two processed Itpa pseudogenes as well as the Itpa gene itself with introns, located on chromosome 2F3, which was isolated by a retro-recombination method. We also identified three types (A, B, C) of Itpa transcripts in mouse tissues. The processed Itpa gene-like sequence located on chromosome 2E1 has a complete open reading frame for exactly the same polypeptide as ITPA encoded by the type A transcript, with a polyadenylation signal. However, no transcribed sequence derived from the Itpa gene-like sequence was detectable in any of the mouse tissues examined, thus naming the sequence as Itpa processed pseudogene alpha. The type A Itpa mRNA, which was expressed in all mouse tissues examined, only encodes mouse ITPA polypeptide consisting of 198 amino acid residues with a capacity to hydrolyze dITP into dIMP. Itpa mRNA was detected in all tissues examined, and its expression is especially high in the testis, brain, and thymus. ITPA protein was mostly detected in the cytoplasm, to a lesser extent in the nuclei of neurons in the brain, and also those of hepatocytes, epithelial cells lining the bile duct, and endothelial cells lining the portal vein in the liver.

Alternative Splicing↗
PubMed1999

Efficient antibody diversification by gene conversion in vivo in the absence of selection for V(D)J-encoded determinants.

Antibody diversification in the bursa of Fabricius occurs by gene conversion: pseudogene-derived sequences replace homologous sequences in rearranged immunoglobulin genes. Bursal cells expressing a truncated immunoglobulin mu heavy chain, introduced by retroviral gene transfer, bypass normal requirements for endogenous surface immunoglobulin expression. Immunoglobulin light chain rearrangements in such cells undergo gene conversion under conditions where the products are not selected based on their ability to encode a functional protein. The efficiency with which gene conversion maintains a productive reading frame exceeds 97% under such non-selective conditions. By analysis of donor pseudogene usage we demonstrate that bursal cell development is not driven by a restricted set of antigenic specificities. We further demonstrate that gene conversion can restore a productive reading frame to out-of-frame VJ(L) junctions, providing a rationale for the elimination of cells containing non-productive VJ(L) rearrangements prior to the onset of gene conversion in normal bursal cell development.

Animals↗
PubMed1993

Steroid 21-hydroxylase deficiency: two additional mutations in salt-wasting disease and rapid screening of disease-causing mutations.

A method for genetic diagnosis of steroid 21-hydroxylase deficiency was developed based on allele-specific PCR. With this approach, genotyping of fourteen mutations and diagnosis of homozygous gene deletions can be performed within hours from tissue sampling. One patient with salt-wasting disease had normal genotype at all positions screened. DNA sequencing revealed two novel mutations, a G to C transversion at the conserved splice donor site of intron 7 and a TGG to TAG nonsense mutation at Trp 406 in exon 9. Allele-specific PCR was established also for these mutations and used to screen for their presence in the pseudogene. However, the two novel mutations were not found in at least 34 pseudogenes.

Adrenal Hyperplasia, Congenital↗
PubMedDate not supplied

An ancient RNase H1 splice junction mutant preserved in a 19-million-year-old genetic fossil in ape genomes.

A retroprocessed pseudogene (retropseudogene) descended from the gene encoding ribonuclease (RNase) H1 has been found in ape genomes that preserves a splice junction mutation event that altered the carboxyl-terminal end of the enzyme. The GT --> GC transition mutant at the 5' splice junction of RNase H1 exon 7/intron 7 led to the absence of exon 8 and more than 1 kb of intron 7 sequence being substituted. Comparison of source gene and pseudogene sequences indicates that the retrotranscription event occurred 19 million years ago. Present in these sequences is an in-frame stop and several available polyadenylation signals, suggesting that the mutant allele could have been translated. At the present time, the genetic fossil is the only evidence that the mutation ever occurred, and thus represents an archival marker of an ancient genetic event in primate evolution.

Animals↗
PubMed2003

A transposable element-mediated gene divergence that directly produces a novel type bovine Bcnt protein including the endonuclease domain of RTE-1.

Ruminant Bcnt protein with a molecular mass of 97 kDa (designated p97Bcnt) includes a region derived from the endonuclease domain of a retrotransposable element RTE-1. Human and mouse Bcnt proteins lack the corresponding region but have a highly conserved 82-amino acid region at the C-terminus that is not present in p97Bcnt. By screening a bovine BAC library, we found two more bcnt-related genes: human-type bcnt (h-type bcnt) and its processed pseudogene. Whereas the pseudogene is localized on chromosome 26, both bcntp97 and the h-type bcnt genes are found on bovine chromosome 18, a synteny region of human chromosome 16 on which human BCNT is localized. Complete nucleotide sequencing of the BAC clone reveals that the bcntp97 and h-type bcnt genes are located just 6 kb apart in a tandem manner. The two h-type bcnt and bcntp97genes are active at both the transcriptional level and the protein level. H-type bovine Bcnt is more like human BCNT than p97Bcnt, when compared at their N-terminal regions. However, phylogenetic analysis using the N-terminal region of the bcnt gene family revealed that the duplication of bovine genes occurred within the bovine lineage with significantly accelerated substitution in bcntp97. This acceleration was not ascribed definitely to positive selection. After duplication, one of the bovine bcnt genes recruited the endonuclease domain of an intronic RTE-1 repeat accompanied by the accelerated substitution at the 5'-ORF, resulting in creation of a novel type of Bcnt protein in bovine.

Amino Acid Sequence↗
PubMed2005

Statistical alignment of retropseudogenes and their functional paralogs.

We describe a model for the sequence evolution of a processed pseudogene and its paralog from a common protein-coding ancestor. The model accounts for substitutions, insertions, and deletions and combines nucleotide- and codon-level mutation models. We give a dynamic programming method for calculating the likelihood of homology between two sequences in the model and describe the accompanying alignment algorithm. We also describe how ancestral codons can be computed when the same gene produced multiple pseudogene homologs. We apply our methods to the evolution of human cytochrome c.

Base Composition↗
PubMed2005

A hotspot of gene order rearrangement by tandem duplication and random loss in the vertebrate mitochondrial genome.

Most reported examples of change in vertebrate mitochondrial (mt) gene order could be explained by a tandem duplication followed by random loss of redundant genes (tandem duplication-random loss [TDRL] model). Under this model of evolution, independent loss of genes arising from a single duplication in an ancestral species are predicted, and remnant pseudogenes expected, intermediate states that may remain in rearranged genomes. However, evidence for this is rare and largely scattered across vertebrate lineages. Here, we report new derived mt gene orders in the vertebrate "WANCY" region of four closely related caecilian amphibians. The novel arrangements found in this genomic region (one of them is convergent with the derived arrangement of marsupials), presence of pseudogenes, and positions of intergenic spacers fully satisfy predictions from the TDRL model. Our results, together with comparative data for the available vertebrate complete mt genomes, provide further evidence that the WANCY genomic region is a hotspot for gene order rearrangements and support the view that TDRL is the dominant mechanism of gene order rearrangement in vertebrate mt genomes. Convergent gene rearrangements are not unlikely in hotspots of gene order rearrangement by TDRL.

Amphibians↗
PubMed1991

Compilation of 5S rRNA and 5S rRNA gene sequences.

This is an update for the 5S rRNA sequences of the BERLIN RNA DATABANK last published in 1990 (1). The new entry consists of 25 eubacterial and 2 eukaryotic 5S rRNA sequences and 10 plant 5S rRNA pseudogenes (Table 1). Thus the BERLIN RNA DATABANK contains as of February 1, 1991 the 5S rRNA sequences of 44 archaebacteria, 292 eubacteria, 20 plastids, 6 mitochondria, 321 eukaryotes and 21 eukaryotic pseudogenes. The BERLIN RNA DATABANK uses the format of the EMBL Nucleotide Sequence Data Library complemented by a Sequence Alignment (SA) field including secondary structure information.

Bacteria↗
PubMed2003

The sequence and analysis of Trypanosoma brucei chromosome II.

We report here the sequence of chromosome II from Trypanosoma brucei, the causative agent of African sleeping sickness. The 1.2-Mb pairs encode about 470 predicted genes organised in 17 directional clusters on either strand, the largest cluster of which has 92 genes lined up over a 284-kb region. An analysis of the GC skew reveals strand compositional asymmetries that coincide with the distribution of protein-coding genes, suggesting these asymmetries may be the result of transcription-coupled repair on coding versus non-coding strand. A 5-cM genetic map of the chromosome reveals recombinational 'hot' and 'cold' regions, the latter of which is predicted to include the putative centromere. One end of the chromosome consists of a 250-kb region almost exclusively composed of RHS (pseudo)genes that belong to a newly characterised multigene family containing a hot spot of insertion for retroelements. Interspersed with the RHS genes are a few copies of truncated RNA polymerase pseudogenes as well as expression site associated (pseudo)genes (ESAGs) 3 and 4, and 76 bp repeats. These features are reminiscent of a vestigial variant surface glycoprotein (VSG) gene expression site. The other end of the chromosome contains a 30-kb array of VSG genes, the majority of which are pseudogenes, suggesting that this region may be a site for modular de novo construction of VSG gene diversity during transposition/gene conversion events.

Animals↗
PubMed2005

Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery.

The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.

DNA Transposable Elements↗
PubMed2006

An enhanced MITOMAP with a global mtDNA mutational phylogeny.

The MITOMAP (http://www.mitomap.org) data system for the human mitochondrial genome has been greatly enhanced by the addition of a navigable mutational mitochondrial DNA (mtDNA) phylogenetic tree of approximately 3000 mtDNA coding region sequences plus expanded pathogenic mutation tables and a nuclear-mtDNA pseudogene (NUMT) data base. The phylogeny reconstructs the entire mutational history of the human mtDNA, thus defining the mtDNA haplogroups and differentiating ancient from recent mtDNA mutations. Pathogenic mutations are classified by both genotype and phenotype, and the NUMT sequences permits detection of spurious inclusion of pseudogene variants during mutation analysis. These additions position MITOMAP for the implementation of our automated mtDNA sequence analysis system, Mitomaster.

DNA, Mitochondrial↗
PubMed1988

Construction of a human cytochrome c gene and its functional expression in Saccharomyces cerevisiae.

The nucleotide sequences of a partial cDNA and three pseudogenes of human cytochrome c were determined. The complete nucleotide sequences which encode human cytochrome c were constructed on the basis of one of the pseudogenes by in vitro mutagenesis. The constructed human cytochrome c was functionally expressed in Saccharomyces cerevisiae. The recombinant human cytochrome c was purified and characterized.

Base Sequence↗
PubMed1990

Structural analysis of multiple bovine P-450(11 beta) genes and their promoter activities.

A bovine genomic library was constructed using a cosmid vector, pHC79, and bovine DNA partially digested by EcoRI. Bovine P-450(11 beta) cDNA, pcP-450(11 beta)-2 [Morohashi et al. (1987) J. Biochem. 102,559-568], was used as a probe for screening the genomic library. Ten clones carrying P-450(11 beta) genomic DNA were isolated from 8 x 10(4) colonies and classified into five groups (CB11 beta-1, CB11 beta-3, CB11 beta-7, CB11 beta-20, and CB11 beta-21) according to differences in the restriction endonuclease sites. Nucleotide sequences of amino acid coding regions of the five clones were determined by the dideoxy sequencing method using synthetic nucleotides corresponding to various parts of the cDNA as primers. The nucleotide sequences revealed that three clones, CB11 beta-1, CB11 beta-3, and CB11 beta-21, were pseudogenes. Amino acid sequences coded by the other two clones, CB11 beta-7 and CB11 beta-20, were identical with that coded by a previously described cDNA, pcP-450(11 beta)-3 [Kirita et al. (1988) J. Biochem. 104, 683-686]. The promoter regions of the five clones were introduced in front of chloramphenicol acetyltransferase (CAT) gene of pSV00CAT and used to examine P-450(11 beta) gene regulation in cultured cells. The five recombinant plasmids showed cAMP-responsive CAT activities in Y-1 cells, a cell strain derived from adrenal tumor. The induction rates of the recombinant plasmids carrying the promoters of normal genes, CB11 beta-7 and -20, were larger than those of pseudogenes, CB11 beta-1, -3, and -21. CAT activities expressed by the promoter regions of the normal genes in the presence or absence of cAMP in Y-1 cells were almost equal to that by the promoter region of human P-450(SCC) gene. Though the promoter of the P-450(SCC) gene also showed cAMP-responsive CAT activity in I-10 cells, a cell strain derived from Leyding cell tumor, P-450(11 beta) gene promoter did not express the activity in I-10 cells.

Amino Acid Sequence↗
PubMed1998

Tandem duplication via light-strand synthesis may provide a precursor for mitochondrial genomic rearrangement.

A tandem duplication of the mitochondrial tRNA(Thr) and tRNA(Pro) genes in the amphisbaenian reptile Bipes biporus is the first case reported of a tandem duplication restricted to a single pair of tRNA genes in a vertebrate mitochondrial genome. Such duplications have been predicted, however, as intermediate steps in the evolution of observed mitochondrial genomic rearrangements through errors in light-strand replication. The tandem duplication reported here is evolutionarily associated with displacement of the origin for light-strand replication from its typical location in vertebrate mitochondrial genomes and loss of the dihydrouridine stem from the tRNA(Cys) gene; these factors implicate light-strand replicational errors in the tandem duplication of genic regions. Pseudogene formation in tandemly duplicated sequences appears to be an intermediate step in genomic rearrangement. However, formation of pseudogenes in the Bipes mitochondrial genome occurs in a pattern that precludes subsequent genomic rearrangement. Functional constraints placed on cleavage of mitochondrial transcripts by tRNA genes also may prevent mitochondrial genomic rearrangement.

Animals↗
PubMed1998

The effect of relaxed functional constraints on the photosynthetic gene rbcL in photosynthetic and nonphotosynthetic parasitic plants.

The photosynthetic gene rbcL has been lost or dramatically altered in some lineages of nonphotosynthetic parasitic plants, but the dynamics of these events following loss of photosynthesis and whether rbcL has sustained functionally significant changes in photosynthetic parasitic plants are unknown. To assess the changes to rbcL associated with the loss of functional constraints for photosynthesis, nucleotide sequences from nonparasitic and parasitic plants of Scrophulariales were used for phylogeny reconstruction and character analysis. Plants in this group display a broad range of parasitic abilities, from photosynthetic ("hemiparasites") to nonphotosynthetic ("holoparasites"). With the exception of Conopholis (Orobanchaceae), the rbcL locus is present in all parasitic plants of Scrophulariales examined. Several holoparasitic genera included in this study, including Boschniakia, Epifagus, Orobanche, and Hyobanche, have rbcL pseudogenes. However, the holoparasites Alectra orobanchoides, Harveya capensis, Harveya purpurea, Lathraea clandestina, Orobanche corymbosa, O. fasciculata, and Striga gesnerioides have intact open reading frames (ORFs) for the rbcL gene. Phylogenetic hypotheses based on rbcL are largely in agreement with those based on sequences of the nonphotosynthetic genes rps2 and matK and show a single origin of parasitism, and loss of photosynthesis and pseudogene formation have been independently derived several times in Scrophulariales. The mutations in rbcL in nonparasitic and hemiparasitic plants would result in largely conservative amino acid substitutions, supporting the hypothesis that functional proteins can experience only a limited range of changes, even in minimally photosynthetic plants. In contrast, ORFs in some holoparasites had many previously unobserved missense substitutions at functionally important amino acid residues, suggesting that rbcL genes in these plants have evolved under relaxed or altered functional constraints.

Amino Acid Substitution↗