Pseudogene

About: Pseudogene is a research topic. Over the lifetime, 5528 publications have been published within this topic receiving 336634 citations. The topic is also known as: Ψ & pseudogenes.

Molecular basis of human growth hormone gene deletions

Abstract: Crossover sites resulting from unequal recombination within the human growth hormone (GH) gene cluster that cause GH1 gene deletions and isolated GH deficiency type 1A were localized in nine patients. In eight unrelated subjects homozygous for 6.7-kilobase (kb) deletions, the breakpoints are within two blocks of highly homologous DNA sequences that lie 5' and 3' to the GH1 gene. In seven of these eight cases, the breakpoints map within a 1250-base-pair (bp) region composed of 300-bp Alu sequences of 86% homology and flanking non-Alu sequences that are 600 and 300 bp in length and are of 96% and 88% homology, respectively. In the eighth patient, the breakpoints are 5' to these Alu repeats and are most likely within a 700-bp region of 96% homologous DNA sequences. In the ninth patient homozygous for a 7.6-kb deletion, the breakpoints are contained within a 29-bp perfect repeat lying 5' to GH1 and the human chorionic somatomammotropin pseudogene (CSHP1). Together, these results indicate that the presence of highly homologous DNA sequences flanking GH1 predispose to recurrent unequal recombinational events presumably through chromosomal misalignment.

Evolutionary Rates of Duplicate Genes in Fish and Mammals

Abstract: Recently, much attention has been attracted by the abundance of duplicate genes in teleost fish (Amores et al 1998; Wittbrodt, Meyer, and Schartl 1998) It has been suggested that this abundance reflected an ancestral genome duplication and that it may be related to the great diversity of this group (Vogel 1998) Emphasizing the importance of gene duplication in evolution, Ohno (1970) pointed out that at least one of the two copies may become less constrained by selection and thus be able to evolve toward a new function Hughes and Hughes (1993) tested this hypothesis in the recent tetraploid Xenopus laevis and showed that both duplicate copies evolve at the same rate, with evidence of negative selection on both Our aim was to characterize whether duplicated genes have allowed a further exploration of the adaptative landscape in teleost fish and mammalian genomes For this, we compared all genes for which at least one duplication was characterized either in a teleost fish or in a eutherian mammal Although pseudogenes are relevant to the overall duplication rate, they do not participate in an eventual adaptative role of gene or genome duplication Since we were interested here in functional evolution, we did not take into account duplications which clearly led to the formation of pseudogenes This was done by the exclusion in the HOVERGEN database (Duret, Mouchiroud, and Gouy 1994) of all sequences explicitly declared to be pseudogenes For each of these genes, we compared rates (1) between the two duplicated copies, as in Hughes and Hughes (1993), and (2) between the lineage with the duplication and the lineage without the duplication Indeed, if gene duplication is followed by a relaxation of selective constraint on genes, the resulting copies should evolve faster than their orthologs in other species which were not duplicated The second test should be able to detect a decrease in selection on either or both copies, unlike the first In practice, we build a 2 3 2 contingency table to compare the observed and expected numbers of genes under the hypothesis of independence between the lineage with the duplication and the lineage with the highest substitution rate (mammals or teleost fish) Genes were recovered from the HOVERGEN database (Duret, Mouchiroud, and Gouy 1994), allowing

Global Transcriptional Effects of a Suppressor tRNA and the Inactivation of the Regulator frmR

Abstract: Expression of an amber suppressor tRNA should result in read-through of the 326 open reading frames (ORFs) that terminate with amber stop codons in the Escherichia coli genome, including six pseudogenes. Abnormal extension of an ORF might alter the activities of the protein and have effects on cellular physiology, while suppression of a pseudogene could lead to a gain of function. We used oligonucleotide microarrays to determine if any effects were apparent at the level of transcription in glucose minimal medium. Surprisingly, only eight genes had significantly different expression in the presence of the suppressor. Among these were the genes yaiN, adhC, and yaiM, forming a single putative operon whose likely function is the degradation of formaldehyde. Expression of wild-type yaiN was shown to result in repression of the operon, while a suppression-mimicking allele lacking the amber stop codon and extended 7 amino acids did not. The operon was shown to be induced by formaldehyde, and the genes have been renamed frmR, frmA, and frmB, respectively.

Evolution of Killer Cell Ig-Like Receptor (KIR) Genes: Definition of an Orangutan KIR Haplotype Reveals Expansion of Lineage III KIR Associated with the Emergence of MHC-C

Abstract: Orangutan ( Pongo pygmaeus ) MHC-C appears less evolved than human HLA-C: Popy-C is not fixed and its alleles encode only one (C1) of the two motifs for killer cell Ig-like receptor (KIR) ligands. To assess the structure and complexity of the orangutan KIR locus, the complete nucleotide sequence of an orangutan KIR haplotype was determined. The PopyKIR locus is flanked by LILR and FCAR and consists of seven genes and pseudogenes, two novel and five corresponding to known cDNA. Distinguishing all KIRs in this rapidly evolving KIR locus from the KIR3DX1 gene is an LTR33A/MLT1D element in intron 3. These two forms of KIR represent lineages that originated by duplication of a common ancestor. The conserved, framework regions of primate KIR loci comprise the 5′ part of a lineage V KIR , the 3′ part of a pseudogene, the complete 2DL4 gene, and the 3′ part of a lineage II KIR . Although previously defined PopyKIR2DL4 alleles contain premature termination codons, the sequenced haplotype’s PopyKIR2DL4 allele encodes a full-length protein. A model for KIR evolution is proposed. Distinguishing the orangutan KIR haplotype from the proposed common ancestor of primate KIR haplotypes is an increased number to give three lineage III KIR genes in the centromeric part of the locus, the site for most human lineage III genes encoding HLA-C specific KIR. Thus, expansion of lineage III KIR is associated with emergence of MHC-C .