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At least 523 records · Page 29Linked to original sources
PubMed1997

Conserved mutations in human ferritin H pseudogenes: a second functional sequence or an evolutionary quirk?

This paper describes a search for a second functional human ferritin H gene in a collection of genomic clones. Nine new H-like sequences have been mapped to chromosomes 1p22-31, 1q32-42, 2q32-33, 3q21-23, 13q12, 14, 17p11-pter and X. These were examined for evidence of possible functionality by sequencing and by searching for possible introns. All except an uncharacterized sequence on chromosome 13 appear to be processed pseudogenes. However, nearly all share several conserved differences with the known functional sequence. These differences occur at regions of unusual structure. It is not known whether these sequences are derived from a second functional gene or from site-specific mutations in the generation of pseudogenes from the known functional gene. We also show that several hominoids contain H gene families with similar complexities to humans and that most of the human genes have counterparts in chimpanzees and gorillas.

Animals↗
PubMed2000

Characterization and chromosomal mapping of a human Necdin pseudogene.

The necdin gene is expressed predominantly in postmitotic neurons and encodes a growth suppressor that interacts with the transcription factors E2F1 and p53. Human necdin gene (NDN) is maternally imprinted and located in Prader-Willi syndrome deletion region 15q11.2-q12. We isolated an NDN homologous sequence from a human genomic DNA library. The homologous sequence is overall 83% identical with necdin cDNA sequence, and possesses a short poly(A) stretch at the 3' end and direct repeats at both ends. Expression of the homologous sequence, which lacks a 5' promoter sequence, was undetected in cultured human cell lines. We mapped this sequence to chromosome 12q14-q21.1 by fluorescence in situ hybridization. These characteristics of the NDN-homologous sequence are consistent with those of processed pseudogenes. The information about the necdin pseudogene in the human genome will be useful for genetic studies on NDN-associated neurogenic disorders.

Base Sequence↗
PubMed2000

A new family of genes and pseudogenes potentially expressing testis- and brain-specific leucine zipper proteins in man and mouse.

We have characterized a new mouse gene highly transcribed in the testis, and a derived intronless gene expressed in the embryo. The latter gene is present in Mus musculus domesticus and in Mus musculus castaneus but is absent in Mus spretus. The sequencing of different clones from a testis cDNA library reveals a complex transcriptional regulation for the intron-containing gene. The use of several promoters, alternative splicing and trans-splicing, and of two different polyadenylation sites account for the diversity. The different cDNAs encode proteins with features of basic helix-loop-helix leucine zipper (bHLH-ZIP) DNA-binding factors with homology to a new brain-specific factor. The presence of multiple CK2 and PKC phosphorylation sites suggests that their activity may be regulated by phosphorylation. In man, a pseudogene, apparently derived from the same transcript as in mouse and showing 90% homology in the coding region, is present within an intron of another gene. Interestingly, although the human pseudogene is highly mutated in human, in the mouse it has only four nucleotide changes compared with the cDNA of origin, and is still capable of encoding a protein.

Alternative Splicing↗
PubMed2001

p53 Pseudogene dating: identification of the origin of laboratory mice.

Mutations were accumulated with a wide variety in the p53 pseudogene of various wild mouse species and subspecies captured at different localities, as extensively observed in the exon 4 - exon 5 region. The rate of mutation accumulation in the mouse p53 pseudogene was estimated to be 1.4-2.1x10(-8) mutations/bp/year, which is 20-30 times faster than that of the functional p53 and makes the dating possible for the time range of 10(6) years or more. From comparison of the mutation spectrum, the origin of laboratory mice was identified to one of two M. m. domesticus groups.

Animals↗
PubMed2001

The murine genome contains one functional gene and two pseudogenes coding for the 16 kDa proteolipid subunit of vacuolar H(+)-ATPase.

We cloned the genomic genes encoding the murine 16 kDa subunit (proteolipid, PL16) of vacuolar H(+)-ATPase (V-ATPase) and determined their nucleotide sequences. At least three independent genes were found in the murine genome. One gene consisted of three exons and was largely identical in sequence to that of PL16 cDNA reported previously (Hanada et al., Biochem. Biophys. Res. Commun. 176 (1991) 1062). In the 5'-flanking region of this gene, several possible transcriptional cis-elements were found. TATA and CAAT sequences were not found, which is characteristic for promoters of house-keeping genes. The other two genes identified did not contain introns. One of these genes had an open reading frame that potentially encoded PL16 but contained six amino acid substitutions and a frame-shift mutation that would result in a truncated protein unable to participate in V-ATPase activity. The other gene had the same sequence in the reading frame as that in the cDNA. However, this gene contained a polyA sequence at the same position where polyA is normally added to mRNA. The gene also had 15 bp repetitive sequences near the transcription initiation site and next to the polyA sequence. These observations suggest that this gene may have been generated by the insertion of reverse-transcribed double-stranded cDNA, as is usually observed for pseudogenes. In conclusion, there is a single functional PL16 gene and two pseudogenes in the murine genome. It is unlikely that PL16 isoforms contribute to variation in V-ATPase function.

Amino Acid Sequence↗
PubMed2002

Characterization of the mtTFA gene and identification of a processed pseudogene in rat.

Mitochondrial DNA replication and transcription are regulated from essential nucleus-encoded components that interact with the mitochondrial (mt) D-loop region. Among these there is the mitochondrial transcription factor A (mtTFA or Tfam). We have determined the sequence of the cDNA mtTFA in rat and have demonstrated that the gene has a mosaic organization with six introns whose sizes we have calculated. A differential splicing transcript lacking exon 5 has been detected in all assayed tissues and represents 9.85% of the full length transcript. Beside the gene which is homologous to the one found in man and mouse, rat nuclear genome contains at least 12 copies of this gene or genome fragments with high similarity to mtTFA. We have determined the sequence of one of these copies. This resulted to have 76.26% similarity to the active gene but to lack introns, suggesting it might be a processed pseudogene. RT-PCR experiments have demonstrated that this pseudogene (psi mtTFA) is transcribed in liver tissue.

Alternative Splicing↗
PubMed2002

Genomic structure of newly identified paralogue of RNA helicase II/Gu: detection of pseudogenes and multiple alternatively spliced mRNAs.

RNA helicase II/Gu (RH-II/Gu or DDX21) is a DEAD-box enzyme that localizes to the nucleoli and may be involved in ribosomal RNA synthesis or processing. It has two paralogues, RH-II/Gualpha and RH-II/Gubeta, both genes of which are on chromosome 10. Their similar genomic structures suggest the two genes arose by gene duplication. Both genes are expressed at higher levels in some normal human tissues compared to matching tumor tissues. Pseudogenes for RH-II/Gubeta exist on chromosomes 2, 3 and 4. No pseudogene was identified for RH-II/Gualpha. Both exon inclusion and exon skipping were found to post-transcriptionally regulate RH-II/Gubeta gene expression. No alternative splicing was identified for RH-II/Gualpha. Overall, the results suggest that the two paralogues of RH-II/Gu arose by gene duplication but the resulting genes are differentially regulated.

3T3 Cells↗
PubMed2002

Characterization of the mouse hnRNP A2/B1/B0 gene and identification of processed pseudogenes.

The mouse hnRNP A2/B1/B0 gene has been cloned using a PCR-based strategy and sequenced. Analysis of this sequence showed that the gene organization closely follows that of the human orthologue with 12 exons and 11 introns. The hnRNP A2/B1/B0 gene gives rise to four splice variants through alternative splicing of exons 2 and 9. RT-PCR assays indicated that all splice variants were expressed in mouse brain, skin, and stomach tissues of varying ages, although their ratios to one another varied with age and tissue type. We also identified a small subset of all polyadenylated splice variants that included intron 11, which shows 94% sequence identity between human and mouse. Several processed pseudogenes were identified in the mouse genome. A search of the mouse genome databases located five pseudogenes, four of which are presumed to be non-functional because of the presence of premature stop codons, large deletions or rearrangements within the coding region. The fifth, which possesses putative promoter elements and has a coding sequence identical to that of the hnRNP A2 mRNA variant, may be functional.

Alternative Splicing↗
PubMed1997

Identification of a human heart FABP pseudogene located on chromosome 13.

The fatty acid-binding proteins (FABPs) constitute a conserved group of cytosolic low molecular mass proteins, which consists of several types: liver, heart, myelin, epidermal, adipocyte, brain, intestinal and ileal type. The FABP gene structure is well conserved during evolution and exhibits a four-exon/three-intron structure. In the past, multiple hybridizing fragments were detected upon Southern blot analysis using heart FABP (H-FABP) cDNA as a probe. The origin of these fragments was not clear. We screened a human genomic library and isolated an intronless gene (FABP3-ps) with 85% similarity to the human H-FABP cDNA and high similarity (76 and 79%) to the H-FABP cDNAs of mouse and bovine, respectively. By means of fluorescence in situ hybridization this processed pseudogene could be assigned chromosome 13q13-q14, whereas the gene for human H-FABP (FABP3) resides on chromosome 1p32-p33. No expression of the processed pseudogene could be detected in skeletal muscle or fetal brain.

Amino Acid Sequence↗
PubMed1992

The human ubiquitin/52-residue ribosomal protein fusion gene subfamily (UbA52) is composed primarily of processed pseudogenes.

Two members of the human ubiquitin gene subfamily encoding ubiquitin fused to a 52-residue ribosomal protein (UbA52) were cloned, sequenced, and analyzed. Both were found to be processed (reverse-transcribed) pseudogenes, containing several nucleotide substitutions and deletions that severely disrupt their potential open-reading frames. Genomic hybridization analysis using probes derived from a functional UbA52 gene (UBA52) suggests that the UbA52 subfamily consists of one intron-containing, transcriptionally active gene and approximately eight processed pseudogenes, a feature characteristic of mammalian ribosomal protein gene families.

Base Sequence↗
PubMed1993

Human Zn-alpha 2-glycoprotein: complete genomic sequence, identification of a related pseudogene and relationship to class I major histocompatibility complex genes.

The human gene (AZGP1) encoding Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a protein present in several biological fluids and produced by a subtype of breast carcinomas, has been cloned and its complete nucleotide sequence determined. The gene spans over 9.7 kb, and its overall organization and nucleotide sequence are very similar to those of the first four exons of class I MHC genes. However, the Zn-alpha 2-gp gene differs from these genes in several significant ways. It lacks the coding information for the transmembrane and cytoplasmic domains typical of MHC genes, which is consistent with its presence as a soluble protein in different physiological and pathological fluids. In addition, it contains a high density of repetitive sequences, including Alu, MER, and MIR elements, which are not present at equivalent positions in class I MHC genes. Finally, its 5'-flanking region lacks the class I MHC regulatory complex and the interferon consensus sequence characteristic of class I MHC genes. These findings may explain the different expression pattern of Zn-alpha 2-gp and class I MHC genes in human tissues. Southern blot hybridization of DNA from several species with a cDNA probe indicated that Zn-alpha 2-gp genes are present in a wide variety of animal species, including monkey, rat, mouse, dog, cow, and rabbit. The human genome also contains a putative Zn-alpha 2-gp pseudogene that has been isolated and partially characterized. This pseudogene has an intron-exon organization identical to that of the functional gene, but it presents two deleterious mutations in the third exon that lead to the appearance of premature stop codons. Finally, considering the lack of polymorphism in the Zn-alpha 2-gp gene in comparison with MHC genes, putative roles for this human glycoprotein in the transport of nonpolymorphic substances or in intercellular recognition processes are proposed.

Amino Acid Sequence↗
PubMed2003

RT-PCR for the pseudogene-free amplification of the glyceraldehyde-3-phosphate dehydrogenase gene (gapd).

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an enzyme which catalyses the conversion of glyceraldehyde-3-phosphate to 1,3 diphosphoglycerate. It is considered to be constitutively expressed in all cells, and as such the gene for GAPDH (gapd) is commonly used as a benchmark reference in expression studies. However, previous investigations have demonstrated that gapd may show altered gene expression in a number of disease states and under certain experimental conditions, suggesting that results of experiments using gapd as a control should be interpreted with caution. Furthermore, consideration must be given to the potential co-amplification of pseudogenes of gapd during RT-PCR. Here, we describe a method to avoid the amplification of contaminating pseudogenes through the design of primers that bind only to genuine gapd mRNA transcript.

Base Sequence↗
PubMed1996

A quick, direct method that can differentiate expressed mitochondrial genes from their nuclear pseudogenes.

Direct sequencing of mitochondrial DNA (mtDNA) following amplification using the polymerase chain reaction (PCR) has found widespread use in population genetic and phylogenetic research over the past few years. Recently, nuclear copies of mitochondrial genes have been reported in diverse eukaryotic species, often confounding such research (reviewed in [2,3]). Under certain circumstances, nuclear pseudogenes can be amplified more efficiently than the intended mtDNA target, even when using as template mtDNA that has been purified by gradient centrifugation. If the transfer of the gene copy to the nucleus happened recently, it can be difficult-if not impossible-to identify the legitimate mitochondrial sequence. Here, we present a simple method that can identify expressed mitochondrial genes, using the cytochrome b gene of the particularly problematical proboscis monkey as an example. Because mtDNA is transcribed and processed into polyadenylated mRNAs reverse transcription coupled to PCR can be used to amplify the expressed mitochondrial version. This method produced an unambiguous sequence for the proboscis monkey mitochondrial cytochrome b gene; in contrast, traditional DNA-based PCR methods produced ambiguous sequence, because many nuclear pseudogenes were present. Phylogenetic analysis of the cytochrome b gene suggests that the proboscis monkey groups with the Asian langurs, rather than forming a sister taxon to all Asian and African colobines as was previously suggested. Reverse transcriptase-coupled PCR should be applicable to many other cases of nuclear transfer of mtDNA, including those involving ribosomal genes.

Animals↗
PubMed2001

Where are the pseudogenes in bacterial genomes?

Most bacterial genomes have very few pseudogenes; notable exceptions include the genomes of the intracellular parasites Rickettsia prowazekii and Mycobacterium leprae. As DNA can be introduced into microbial genomes in many ways, the compact nature of these genomes suggests that the rate of DNA influx is balanced by the rate of DNA deletion. We propose that the influx of dangerous genetic elements such as transposons and bacteriophages selects for the maintenance of relatively high deletion rates in most bacteria; the sheltered lifestyle of intracellular parasites removes this threat, leading to reduced deletion rates and larger pseudogene loads.

Bacteriophages↗
PubMed1998

A human HP1 pseudogene maps to chromosome 11p14.

The chromo multigene superfamily encodes numerous proteins involved in chromatin structure or organization. The prototypical member of this superfamily is HP1 of Drosophila melanogaster. We now present the sequence of a human HP1Hs gamma pseudogene and assign it to chromosome 11p14 by radiation hybrid mapping. The coding regions of at least three other human genes for HP1 orthologues and another pseudogene are very similar in sequence. These results demonstrate that HP1-type sequences have been duplicated multiple times in the mammalian genome.

Base Sequence↗
PubMed2000

Human LINE retrotransposons generate processed pseudogenes.

Long interspersed elements (LINEs) are endogenous mobile genetic elements that have dispersed and accumulated in the genomes of higher eukaryotes via germline transposition, with up to 100,000 copies in mammalian genomes. In humans, LINEs are the major source of insertional mutagenesis, being involved in both germinal and somatic mutant phenotypes. Here we show that the human LINE retrotransposons, which transpose through the reverse transcription of their own transcript, can also mobilize transcribed DNA not associated with a LINE sequence by a process involving the diversion of the LINE enzymatic machinery by the corresponding mRNA transcripts. This results in the 'retroposition' of the transcribed gene and the formation of new copies that disclose features characteristic of the widespread and naturally occurring processed pseudogenes: loss of intron and promoter, acquisition of a poly(A) 3' end and presence of target-site duplications of varying length. We further show-by introducing deletions within either coding sequence of the human LINE-that both ORFs are necessary for the formation of the processed pseudogenes, and that retroviral-like elements are not able to produce similar structures in the same assay. Our results strengthen the unique versatility of LINEs as genome modellers.

Animals↗
PubMed2000

Dichotomy of single-nucleotide polymorphism haplotypes in olfactory receptor genes and pseudogenes.

Substantial efforts are focused on identifying single-nucleotide polymorphisms (SNPs) throughout the human genome, particularly in coding regions (cSNPs), for both linkage disequilibrium and association studies. Less attention, however, has been directed to the clarification of evolutionary processes that are responsible for the variability in nucleotide diversity among different regions of the genome. We report here the population sequence diversity of genomic segments within a 450-kb cluster of olfactory receptor (OR) genes on human chromosome 17. We found a dichotomy in the pattern of nucleotide diversity between OR pseudogenes and introns on the one hand and the closely interspersed intact genes on the other. We suggest that weak positive selection is responsible for the observed patterns of genetic variation. This is inferred from a lower ratio of polymorphism to divergence in genes compared with pseudogenes or introns, high non-synonymous substitution rates in OR genes, and a small but significant overall reduction in variability in the entire OR gene cluster compared with other genomic regions. The dichotomy among functionally different segments within a short genomic distance requires high recombination rates within this OR cluster. Our work demonstrates the impact of weak positive selection on human nucleotide diversity, and has implications for the evolution of the olfactory repertoire.

Alleles↗
PubMed1992

Structure of the X-linked Kallmann syndrome gene and its homologous pseudogene on the Y chromosome.

The gene for the X-linked Kallmann syndrome (KAL), a developmental disorder characterized by hypogonadotropic hypogonadism and anosmia, maps to Xp22.3 and has a homologous locus, KALP, on Yq11. We show here that KAL consists of 14 exons spanning 120-200 kilobases that correlate with the distribution of domains in the predicted protein including four fibronectin type III repeats. The KALP locus reveals several large deletions and a number of small insertions, deletions and base substitutions which indicate it is a non-processed pseudogene. The sequence divergence between KAL and KALP in humans, and the chromosomal location of KAL homologous sequences in other primates, suggest that KALP and the steroid sulphatase pseudogene on Yq11 were involved in the same rearrangement event on the Y chromosome during primate evolution.

Amino Acid Sequence↗