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At least 19 recordsLinked to original sources
PubMed1989

Structure of the goat psi beta y beta-globin pseudogene. Analysis of goat pseudogene evolutionary patterns.

The 12-member beta-globin gene locus of the goat contains three beta(adult)-type pseudogenes, one in each of three four-gene subsets of the locus. We have determined the complete nucleotide sequence of psi beta y, the pseudogene present in the most downstream four-gene subset, which also contains the functional fetal gene, beta F. psi beta y contains, throughout its length, numerous incapacitating mutations in common with the previously sequenced goat psi beta x and psi beta z pseudogenes consistent with the model that all were descended from a common pseudogene ancestor which became defective prior to the expansion of the beta-globin locus in the goat lineage. Evolutionary analysis of the psi beta y sequence in comparison to psi beta x and psi beta z provides evidence that nucleotide substitutions were fixed in a random manner within these pseudogenes with respect to polarity, coding versus non-coding regions, and replacement sites versus silent sites. However, substitutions appear to have accumulated asymmetrically between different pseudogenes in a manner that provides evidence for partial gene conversion. Moreover, the presence of deletions in goat psi beta y, which are also observed in the cow pseudogene psi 2, but not in the cow psi 1 pseudogene, indicate that goat psi beta y and cow psi 2 are orthologous but cow psi 1 actually arose prior to the goat/cow divergence. The authentic goat orthologue to cow psi 1 temporarily existed in the goat lineage but was deleted, probably prior to the divergence of goats and sheep.

Amino Acid Sequence↗
PubMed1986

Molecular evolution of mammalian lactate dehydrogenase-A genes and pseudogenes: association of a mouse processed pseudogene with a B1 repetitive sequence.

A mouse genomic clone containing a lactate dehydrogenase-A (LDH-A) processed pseudogene and a B1 repetitive element was isolated, and a nucleotide sequence of approximately 3 kb was determined. The pseudogene and B1 element are flanked by perfect 13-bp repeats, and the B1 sequence starts at 14 nucleotides 3' to the presumptive polyadenylation signal of the pseudogene. The nucleotide sequences of the LDH-A genes and processed pseudogenes from mouse, rat, and human were compared, and a phylogenetic tree was constructed. The rate and pattern of nucleotide substitutions in the LDH-A pseudogenes are similar to previously reported results (Li et al. 1984). The average rate of nucleotide substitutions in the LDH-A pseudogenes is 4.3 X 10(-9)/site/year. The substitutions of C----T and G----A are most frequent, and A----G substitutions are relatively high. The rate of synonymous substitutions in the LDH-A genes is 5.3 X 10(-9), which is not significantly higher than the average rate of 4.7 X 10(-9) for 35 mammalian genes. The rate of nonsynonymous substitutions in the LDH-A genes is 0.20 X 10(-9), which is considerably lower than the average rate of 0.88 X 10(-9) for 35 mammalian genes. Thus, the mammalian LDH-A gene appears to be highly conserved in evolution.

Animals↗
PubMed1992

The rat genome contains a p53 pseudogene: detection of a processed pseudogene using PCR.

The p53 gene is the most frequently mutated gene in human cancer. Our investigation of this gene in radiation-induced tumors led to the discovery of a processed pseudogene in the rat genome. We amplified eight coding exons of the p53 gene using rat liver DNA as template, and, in each case, one major amplification product was apparent on agarose gels. When we selected primers to amplify fragments containing more than one exon, two major products were apparent. In each case, the size of the larger amplification product was consistent with that of the expected p53 fragment. The sizes of the shorter amplification products suggested that these fragments are amplified from a processed p53 pseudogene. When the blotted fragments were probed with sequences internal to the amplification primers, both the gene and putative pseudogene fragments were seen. Sequences of the shorter coamplicons have high homology with the p53 cDNA and cross intron splice junctions. These findings suggest that the rat genome contains a processed p53 pseudogene. The data demonstrate the usefulness of the polymerase chain reaction for revealing processed pseudogenes, and suggest that the pseudogene can be used as an internal control when amplifying the rat p53 gene.

Animals↗
PubMed1992

Examination of four HLA class I pseudogenes. Common events in the evolution of HLA genes and pseudogenes.

The HLA class I gene family in lymphoblastoid cell line 721 has been studied in detail and a number of sequences in addition to the classical genes have been identified. The cloning, characterization, and nucleotide sequences of four sequences, all full length HLA class I pseudogenes, are described in this report. These pseudogenes, contained within 5.4-, 5.9-, 7.0-, and 9.2-kb HindIII fragments, each have the class I exon-intron structure as well as class I homology in their 5' and 3' flanking regions. However, all four sequences have one or more substitutions that perturb the coding region, leaving little doubt that they are in fact pseudogenes. Comparisons among these sequences and the HLA class I genes revealed that their homology with the class I genes is patchwork. Thus, although some regions have diverged, other contiguous intron-exon sequences are highly conserved. Comparisons in the 5' regions indicate that the pseudogene promoters more closely resemble the classical HLA promoters than the nonclassical promoters as none of the unique structural features found in the HLA-E, -F, or -G regulatory regions are present in any of the pseudogene promoters. Further comparisons revealed that at least two putative gene conversion events, similar to those hypothesized to have occurred in the evolution of some HLA genes, may have occurred in the evolution of some of the pseudogenes. These and other hypothetical events in the evolution of the class I gene family are discussed.

Base Sequence↗
PubMedDate not supplied

Unusual evolutionary conservation of 5S rRNA pseudogenes in Aspergillus nidulans: similarity of the DNA sequence associated with the pseudogenes with the mouse immunoglobulin switch region.

All Aspergillus nidulans 5S rRNA pseudogenes known so far are the result of integration of an approx. 0.2-kbp-long DNA sequence into the 5S rRNA genes. This sequence, called block C, is present in at least five copies in the A. nidulans genome and seems to be associated either with 5S rRNA genes or pseudogenes. In contrast to the 78% sequence conservation of the C-block in pseudogenes, the truncated 5' halves of the pseudogenes are very highly conserved (96.9-100%). We postulate that the 5S rRNA pseudogenes are still a subject of concerted evolution. The C-block sequence shows similarity to the switch region of the mouse heavy chain immunoglobulin gene. A characteristic motif GGGTGAG is repeated several times in both sequences; the sequence conservation is 63%.

Animals↗
PubMed1992

Identification of a processed pseudogene related to the functional gene encoding the GM2 activator protein: localization of the pseudogene to human chromosome 3 and the functional gene to human chromosome 5.

The GM2 activator protein is an essential substrate cofactor for the hydrolysis of GM2 ganglioside by lysosomal beta-hexosaminidase A (EC 3.2.1.52). There have been conflicting reports as to the chromosomal localization of the gene encoding the activator. We demonstrate here that these conflicts were caused by the presence of a previously unidentified processed activator-pseudogene on chromosome 3, and we confirm a previous ELISA-based localization of the functional activator gene to chromosome 5. Our data indicate that the functional activator locus can still be considered a candidate site for defects causing some forms of spinal muscular atrophy.

Animals↗
PubMed1985

Evolution of the functional human beta-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes.

We have assigned six members of the human beta-actin multigene family to specific human chromosomes. The functional gene, ACTB, is located on human chromosome 7, and the other assigned beta-actin-related sequences are dispersed over at least four different chromosomes including one locus assigned to the X chromosome. Using intervening sequence probes, we showed that the functional gene is single copy and that all of the other beta-actin related sequences are recently generated in evolution and are probably processed pseudogenes. The entire nucleotide sequence of the functional gene has been determined and is identical to cDNA clones in the coding and 5' untranslated regions. We have previously reported that the 3' untranslated region is well conserved between humans and rats (Ponte et al., Nucleic Acids Res. 12:1687-1696, 1984). Now we report that four additional noncoding regions are evolutionarily conserved, including segments of the 5' flanking region, 5' untranslated region, and, surprisingly, intervening sequences I and III. These conserved sequences, especially those found in the introns, suggest a role for internal sequences in the regulation of beta-actin gene expression.

Actins↗
PubMed1985

Processed pseudogenes: characteristics and evolution.

The processed pseudogenes reported to date fall into three categories: those that are a complete copy of the mRNA transcribed from the functional gene, those that are only a partial copy of the corresponding mRNA, and those that contain sequences in addition to those expected to be present in the mRNA. The general structural characteristics of these processed pseudogenes include the complete lack of intervening sequences found in the functional counterparts, a poly A tract at the 3' end, and direct repeats flanking the pseudogene sequence. In all the cases studied, these pseudogenes have been found to be on a different chromosome from their functional counterpart. These characteristics have led investigators to suggest that an RNA intermediate, in many cases the mRNA of the functional gene, is involved in the production of these pseudogenes. The mechanism by which processed pseudogenes arose involves the integration of the mRNA, or its cDNA copy, into a staggered chromosome break, followed by DNA synthesis and repair. I suggest that all the transcripts that gave rise to these pseudogenes were actually produced in the germ line cell. The transcripts that gave rise to the processed pseudogenes that are direct copies of the corresponding mRNA resulted from RNA polymerase II transcription of the functional counterpart. Pseudogenes that are not a direct copy of the corresponding mRNA may have resulted from RNA polymerase III transcription. If this is indeed the case, one need not postulate the involvement of retroviruses to explain the presence of processed pseudogenes corresponding to genes that are not expressed in the germ line. Following the integration event, processed pseudogenes can no longer be transcribed to produce the functional mRNA from which they arose. This inability to be transcribed by RNA polymerase II is not surprising considering that processed pseudogenes seem to be randomly integrated into the genome. Therefore, integration of a processed pseudogene such that RNA polymerase II transcriptional promoters are correctly positioned 5' to the resultant pseudogene is an unlikely event. The presence of processed pseudogenes seems peculiar to mammals. In fact, evolutionary studies indicate that processed pseudogenes are of relatively recent origin. In fact, at least one processed pseudogene, the human DHFR psi 1, has been formed so recently that it is polymorphic.

Animals↗
PubMed1991

Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction.

Structural analysis of the von Willebrand factor gene located on chromosome 12 is complicated by the presence of a partial unprocessed pseudogene on chromosome 22q11-13. The structures of the von Willebrand factor pseudogene and corresponding segment of the gene were determined, and methods were developed for the rapid differentiation of von Willebrand factor gene and pseudogene sequences. The pseudogene is 21-29 kilobases in length and corresponds to 12 exons (exons 23-34) of the von Willebrand factor gene. Approximately 21 kilobases of the gene and pseudogene were sequenced, including the 5' boundary of the pseudogene. The 3' boundary of the pseudogene lies within an 8-kb region corresponding to intron 34 of the gene. The presence of splice site and nonsense mutations suggests that the pseudogene cannot yield functional transcripts. The pseudogene has diverged approximately 3.1% in nucleotide sequence from the gene. This suggests a recent evolutionary origin approximately 19-29 million years ago, near the time of divergence of humans and apes from monkeys. Several repetitive sequences were identified, including 4 Alu, one Line-1, and several short simple sequence repeats. Several of these simple repeats differ in length between the gene and pseudogene and provide useful markers for distinguishing these loci. Sequence differences between the gene and pseudogene were exploited to design oligonucleotide primers for use in the polymerase chain reaction to selectivity amplify sequences corresponding to exons 23-34 from either the von Willebrand factor gene or the pseudogene. This method is useful for the analysis of gene defects in patients with von Willebrand disease, without interference from homologous sequences in the pseudogene.

Amino Acid Sequence↗
PubMed1986

An unusual adenine phosphoribosyltransferase pseudogene is syntenic with its functional gene and is flanked by highly polymorphic DNAs.

A mouse adenine phosphoribosyltransferase (aprt) pseudogene that had previously been recovered from a BALB/c sperm DNA library possessed several unusual features. Its nucleotide sequence, like that of other processed pseudogenes, was colinear with its corresponding mRNA, but it was truncated at its 3' end and lacked a poly(A) tail. The pseudogene was 82% homologous with corresponding regions of the functional gene and had incurred mutations that included transitions, transversions, deletions, and a point insertion. Even though the pseudogene was truncated within the protein-coding region of the corresponding functional gene, it was flanked at both ends by 13-base-pair direct repeats. Curiously, the direct repeats exhibited homology to APRT mRNA at the site of pseudogene divergence. The pseudogene appeared to be common to BALB/c and A/J mice, but it was contained on a 3-kilobase EcoRI fragment in the former strain and a 4.5-kilobase EcoRI fragment in the latter. The BALB/c and apparently the A/J pseudogene both mapped to chromosome 8, which also contains the functional aprt gene. The DNA sequences immediately surrounding the pseudogene in the two strains appeared to be similar, suggesting that the BALB/c and A/J pseudogenes are allelic. However, DNA sequences more distal to the pseudogene in the two strains appeared to vary. Thus, the EcoRI polymorphism was not due to simple loss of an EcoRI site, but was more complex. The pattern of flanking restriction sites was different for each of several enzymes, consistent with extensive DNA rearrangement. Double digests of BALB/c and A/J genomic DNAs revealed complex polymorphisms on both sides of the pseudogene. The results were consistent with insertion, deletion, or other rearrangement of DNA sequences that flank the pseudogene and suggest that this region of mouse chromosome 8 may be a region active for mutation or recombination.

Adenine Phosphoribosyltransferase↗
PubMed1988

Identification of a transcriptionally active pseudogene in the chorion locus of the silkmoth Bombyx mori. Regional sequence conservation and biological function.

We have determined the primary structure of a 3500 base-pair part of the silkmoth chorion locus mapping in a region containing genes of late developmental specificity. This part of the locus was found to harbour a pseudogene related to one of the families of chorion genes encoding high cysteine proteins, HcB. The pseudogene exhibits an overall sequence identity of 84% to the consensus coding region of HcB chorion genes. A 95% identity was observed over a length of 190 base-pairs of its immediate 5' upstream sequences and the corresponding part of the consensus 5'-intergenic sequences of Hc gene pairs, normally encompassing 270 base-pairs. Thus, the pseudogene has retained part of the promoter region that includes sequence elements whose presence is thought to be necessary for transcriptional competence of HcB genes. The pseudogene is also characterized by the elimination of part of its first exon containing most of the 5' untranslated region, the ATG translation initiation codon and part of the signal peptide sequences. Its intron is longer than that of other HcB genes due to the insertion of a copy of a repetitive element that appears to be transcribed by RNA polymerase III. A previously characterized chorion cDNA clone, m2282, representing a rare mRNA sequence of late developmental specificity, was found to be identical to the pseudogene over its entirety spanning 65% of the pseudogene's second exon. Hybridizations of clones spanning a 260,000 base-pair domain of the chorion locus of Bombyx mori and of total genomic DNA to a subfragment of the cDNA clone containing relatively unique sequences, coupled to primer extension experiments, have demonstrated that m2282 mRNA originated from the pseudogene and that the pseudogene transcripts are initiated at the chorion cap site consensus sequence. We conclude that the 5'-flanking sequences retained by the pseudogene encompass elements necessary and adequate for correct transcriptional activation, but may not include those required for quantitative expression of the promoter. Possible reasons for the observed lack of random drift in the 5'-upstream sequences of the pseudogene and the maintenance of a functional promoter in a non-functional gene are discussed on the basis of the observation that elements resembling scaffold attachment sites are present in these sequences.

Amino Acid Sequence↗
PubMed1985

How many processed pseudogenes are accumulated in a gene family?

A simple kinetic model is developed that describes the accumulation of processed pseudogenes in a functional gene family. Insertion of new pseudogenes occurs at rate v per gene and is countered by spontaneous deletion (at rate delta per DNA segment) of segments containing processed pseudogenes. If there are k functional genes in a gene family, the equilibrium number of processed pseudogenes is k(v/delta), and the percentage of functional genes in the gene family at equilibrium is 1/[1 + (v/delta)]. v/delta values estimated for five gene families ranged from 1.7 to 15. This fairly narrow range suggests that the rates of formation and deletion of processed pseudogenes may be positively correlated for these families. If delta is sufficiently large relative to the per nucleotide mutation rate mu (delta greater than 20 mu), processed pseudogenes will show high homology with each other, even in the absence of gene conversion between pseudogenes. We argue that formation of processed pseudogenes may share common pathways with transposable elements and retroviruses, creating the potential for correlated responses in the evolution of processed pseudogenes due to direct selection for control of transposable elements and/or retroviruses. Finally, we discuss the nature of the selective forces that may act directly or indirectly to influence the evolution of processed pseudogenes.

Animals↗
PubMed1991

Primate DRB6 pseudogenes: clue to the evolutionary origin of the HLA-DR2 haplotype.

The HLA-DR2 haplotype contains three beta-chain encoding DRB genes and one alpha-chain encoding DRA gene. Of the three DRB genes, two are presumably functional (HLA-DRB1 and HLA-DRB5), whereas the third (HLA-DRBVI) is a pseudogene. A pseudogene closely related to HLA-DRBVI is present in the chimpanzee (Patr-DRB6) and in the gorilla (Gogo-DRB6). We sequenced the HLA-DRBVI and Patr-DRB6 pseudogenes (all exons and most of the introns), and compared the sequence to that of the Gogo-DRB6 gene (of which only the exon sequence is available). All three pseudogenes seem to lack exon 1 and contain other deletions responsible for shifts in the translational reading frame. At least the HLA-DRBVI pseudogene, however, seems to be transcribed nevertheless. The chimpanzee pseudogene contains two inserts in intron 2, one of which is an Alu repeat belonging to the Sb subfamily, while the other remains unidentified. These inserts are lacking in the human gene. A comparison with sequences published by other investigators revealed the presence of the HLA-DRBVI pseudogene also in the DR1 and DRw10 haplotypes. Measurements of genetic distances indicate DRB6 to be closely related to the DRB2 pseudogene and to the HLA-DRB4 functional gene. In humans, gorillas, and chimpanzees, the DRB6 pseudogene is associated with the same functional gene (DRB5) indicating that this linkage disequilibrium is at least six million years old and that DR2 is one of the oldest DR haplotypes in higher primates.

Animals↗
PubMed1988

Characterization, evolutionary relationships, and chromosome location of processed mouse HPRT pseudogene.

Studies on a cell line with amplified copies of the mouse hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene and HPRT gene transfer experiments revealed the existence of a nonfunctional HPRT-related sequence in the mouse genome. This sequence was isolated and found to be a processed HPRT pseudogene. With the exception of a small internal deletion, the pseudogene is believed to comprise a complete reverse transcript of HPRT mRNA, although the 3' end of the pseudogene was lost in the cloning process. A probe from a region flanking the mouse pseudogene was used to investigate the evolutionary relationships of mammalian HPRT pseudogenes. The pseudogenes in mouse and Chinese hamster appear to have a common origin, but no homology to any of the four known human HPRT pseudogenes was detected. A pseudogene-linked restriction fragment length polymorphism was used to map the pseudogene to the distal end of mouse chromosome 17.

Animals↗
PubMed1991

Two closely related kappa variable region pseudogenes pose an evolutionary paradox.

Two pseudogenes belonging to the Igk-V1 variable region group have been isolated from BALB/c mice. The genes share greater than 96.5% identity of nucleotide sequence in a 1800 base pair (bp) region surrounding the coding region, but deletions of 221 bp and 84 bp have removed essential sequences from the two genes. As the deletions are different in the two pseudogenes, they must have occurred independently in each gene during or subsequent to the duplication event which gave rise to the genes from a common ancestral gene. Polymerase chain reaction analysis was used to identify the pseudogenes in inbred strains of mice. BALB/c (Igkc) and AKR (Igka), prototype strains representative of the predominant kappa haplotypes, possess both pseudogenes but no intact copy. Only one of the pseudogenes was present in SJL (Igka). Strains C58, c.C58 (Igkd) and NZB (Igkb) possessed an intact version of the gene. This distribution of haplotypes is consistent with a close linkage of the pseudogenes with other Igk-V1 genes on chromosome 6. The translated amino acid sequence of the pseudogenes indicates that prior to their acquiring deletions they encoded typical Igk-V1 variable regions except for an unusual FR2 region, in which the conserved proline at position 44 is replaced by leucine and the normally hydrophobic position 36 was occupied by histidine. Possible mechanisms to explain the occurrence of deletions in both of the pseudogenes in the recent evolution of BALB/c are discussed. One explanation would be that the two genes were already nonfunctional at the time of the duplication so that the subsequent deletions represent neutral events which became fixed in the inbred strains by a process of genetic drift. Alternatively, if the genes were functional at the time of duplication, their rapid loss due to deletion events suggests that negative selection may have acted to eliminate the genes from the V-region repertoire.

Alleles↗
PubMed1989

Deletions in processed pseudogenes accumulate faster in rodents than in humans.

The relative rates of point nucleotide substitution and accumulation of gap events (deletions and insertions) were calculated for 22 human and 30 rodent processed pseudogenes. Deletion events not only outnumbered insertions (the ratio being 7:1 and 3:1 for human and rodent pseudogenes, respectively), but also the total length of deletions was greater than that of insertions. Compared with their functional homologs, human processed pseudogenes were found to be shorter by about 1.2%, and rodent pseudogenes by about 2.3%. DNA loss from processed pseudogenes through deletion is estimated to be at least seven times faster in rodents than in humans. In comparison with the rate of point substitutions, the abridgment of pseudogenes during evolutionary times is a slow process that probably does not retard the rate of growth of the genome due to the proliferation of processed pseudogenes.

Animals↗
PubMed1990

Human lactate dehydrogenase-B processed pseudogene: nucleotide sequence analysis and assignment to the X-chromosome.

Two human genomic clones containing the lactate dehydrogenase-B processed pseudogene were isolated from two patients deficient in lactate dehydrogenase-B isozyme. The sequences of 3,287 nucleotides, including the pseudogenes and its flanking regions, from both clones were found to be identical except for three differences in the pseudogenes. The sequences of 1,286 nucleotides from these two pseudogenes exhibited 93% homology with the cDNA sequence of the lactate dehydrogenase-B functional gene, and the pseudogene contained 75/76 base substitutions, 11/12 single-base deletions, and 5 single-base insertions. This pseudogene was mapped to the x-chromosome by dot-blot analysis using a probe for the pseudogene or its 5' flanking sequence.

Base Sequence↗
PubMed1990

The processed pseudogene of mouse thymidine kinase is active after transfection.

Aside of the gene coding for cytoplasmic thymidine kinase, the genome of mouse cells carries two pseudogenes. Both are inactive in situ. One of the pseudogenes is a processed pseudogene in which a two base pair deletion caused a shift of the reading frame and a shortening of the gene product from the 233 amino acids of thymidine kinase to 177 amino acids in the pseudogene product. We report here that introduction of this pseudogene into LTK- cells gave rise to cells with a thymidine kinase positive phenotype. The transformed cells carried multiple copies of the pseudogene the upstream region of which exhibited low but measurable promoter activity. Replacement of the upstream region of the pseudogene by a promoter of Simian virus 40 or of the mammary tumor virus resulted in high transfection efficiencies and in cell lines exhibiting high thymidine kinase activities.

Animals↗