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.

Mycobacterium leprae: genes, pseudogenes and genetic diversity

Abstract: Leprosy, which has afflicted human populations for millenia, results from infection with Mycobacterium leprae, an unculturable pathogen with an exceptionally long generation time. Considerable insight into the biology and drug resistance of the leprosy bacillus has been obtained from genomics. M. leprae has undergone reductive evolution and pseudogenes now occupy half of its genome. Comparative genomics of four different strains revealed remarkable conservation of the genome (99.995% identity) yet uncovered 215 polymorphic sites, mainly single nucleotide polymorphisms, and a handful of new pseudogenes. Mapping these polymorphisms in a large panel of strains defined 16 single nucleotide polymorphism-subtypes that showed strong geographical associations and helped retrace the evolution of M. leprae.

Epigenetic Silencing May Aid Evolution by Gene Duplication

Abstract: Gene duplication is commonly regarded as the main evolutionary path toward the gain of a new function However, even with gene duplication, there is a loss-versus-gain dilemma: most newly born duplicates degrade to pseudogenes, since degenerative mutations are much more frequent than advantageous ones Thus, something additional seems to be needed to shift the loss versus gain equilibrium toward functional divergence We suggest that epigenetic silencing of duplicates might play this role in evolution This study began when we noticed in a previous publication (Lynch M, Conery JS [2000] Science 291:1151-1155) that the frequency of functional young gene duplicates is higher in organisms that have cytosine methylation (H sapiens, M musculus, and A thaliana) than in organisms that do not have methylated genomes (S cerevisiae, D melanogaster, and C elegans) We find that genome data analysis confirms the likelihood of much more efficient functional divergence of gene duplicates in mammals and plants than in yeast, nematode, and fly We have also extended the classic model of gene duplication, in which newly duplicated genes have exactly the same expression pattern, to the case when they are epigenetically silenced in a tissue- and/or developmental stage-complementary manner This exposes each of the duplicates to negative selection, thus protecting from "pseudogenization" Our analysis indicates that this kind of silencing (i) enhances evolution of duplicated genes to new functions, particularly in small populations, (ii) is quite consistent with the subfunctionalization model when degenerative but complementary mutations affect different subfunctions of the gene, and (iii) furthermore, may actually cooperate with the DDC (duplication-degeneration-complementation) process

The human retinoblastoma gene is imprinted.

Abstract: Genomic imprinting is an epigenetic process leading to parent-of-origin–specific DNA methylation and gene expression. To date, ∼60 imprinted human genes are known. Based on genome-wide methylation analysis of a patient with multiple imprinting defects, we have identified a differentially methylated CpG island in intron 2 of the retinoblastoma (RB1) gene on chromosome 13. The CpG island is part of a 5′-truncated, processed pseudogene derived from the KIAA0649 gene on chromosome 9 and corresponds to two small CpG islands in the open reading frame of the ancestral gene. It is methylated on the maternal chromosome 13 and acts as a weak promoter for an alternative RB1 transcript on the paternal chromosome 13. In four other KIAA0649 pseudogene copies, which are located on chromosome 22, the two CpG islands have deteriorated and the CpG dinucleotides are fully methylated. By analysing allelic RB1 transcript levels in blood cells, as well as in hypermethylated and 5-aza-2′-deoxycytidine–treated lymphoblastoid cells, we have found that differential methylation of the CpG island skews RB1 gene expression in favor of the maternal allele. Thus, RB1 is imprinted in the same direction as CDKN1C, which operates upstream of RB1. The imprinting of two components of the same pathway indicates that there has been strong evolutionary selection for maternal inhibition of cell proliferation.

A Transcriptionally Active Human Type II Gonadotropin-Releasing Hormone Receptor Gene Homolog Overlaps Two Genes in the Antisense Orientation on Chromosome 1q.12

Abstract: GnRH-II peptide hormone exhibits complete sequence conservation across vertebrate species, including man. Type-II GnRH receptor genes have been characterized recently in nonhuman primates, but the human receptor gene homolog contains a frameshift, a premature stop codon (UGA), and a 3' overlap of the RBM8A gene on chromosome 1q.12. A retrotransposed pseudogene, RBM8B, retains partial receptor sequence. In this study, bioinformatics show that the human receptor gene promoter overlaps the peroxisomal protein 11-beta gene promoter and the premature UGA is positionally conserved in chimpanzee. A CGA [arginine (Arg)] occurs in porcine DNA, but UGA is shifted one codon to the 5' direction in bovine DNA, suggesting independent evolution of premature stop codons. In contrast to marmoset tissue RNA, exon- and strand-specific probes are required to distinguish differently spliced human receptor gene transcripts in cell lines (HP75, IMR-32). RBM8B is not transcribed. Sequencing of cDNAs for spliced receptor mRNAs showed no evidence for alteration of the premature UGA by RNA editing, but alternative splicing circumvents the frameshift to encode a two-membrane-domain protein before this UGA. A stem-loop motif resembling a selenocysteine insertion sequence and a potential alternative translation initiation site might enable expression of further proteins involved in interactions within the GnRH system.

Complete nucleotide sequence of the chloroplast genome from the Tasmanian Blue Gum, Eucalyptus globulus (Myrtaceae)

Abstract: The complete nucleotide sequence of the chloroplast genome of the hardwood species Eucalyptus globulus is presented and compared with chloroplast genomes of tree and non-tree angiosperms and two softwood tree species. The 160 286 bp genome is similar in gene order to that of Nicotiana, with an inverted repeat (IR) (26 393 bp) separated by a large single copy (LSC) region of 89 012 bp and a small single copy region of 18 488 bp. There are 128 genes (112 individual gene species and 16 genes duplicated in the inverted repeat) coding for 30 transfer RNAs, 4 ribosomal RNAs and 78 proteins. One pseudogene (-infA) and one pseudo-ycf (-ycf15) were identified. The chloroplast genome of E. globulus is essentially co-linear with that of another hardwood tree species, Populus trichocarpa, except that the latter lacks rps16 and rpl32, and the IR has expanded in Populus to include rps19 (part of the LSC in E. globulus). Since the chloroplast genome of E. globulus is not significantly different from other tree and non-tree angiosperm taxa, a comparison of hardwood and softwood chloroplasts becomes, in essence, a comparison of angiosperm and gymnosperm chloroplasts. When compared with E. globulus, Pinus chloroplasts have a very small IR, two extra tRNAs and four additional photosynthetic genes, lack any functional ndh genes and have a significantly different genome arrangement. There does not appear to be any correlation between plant habit and chloroplast genome composition and arrangement.