Here, we merge overlapping and succeeding BLAST impacts into a continuous pseudogenetic structure (Fig. 1C). We first analyze the overlapping BLAST moves within a single disjoint set and merge them into a single „superhit” or „pseudo-exon”. We then select adjacent disjoint result sets that match the same query protein. Based on the distance between the hits on the chromosome (Gc in Fig. 1C) and the distance on the interrogation protein (Gq), we determine whether these fused hits belong to the same pseudogenetic structure. These Gc gaps can be caused by (1) low-complexity or highly decomposed regions of the pseudogene that are removed by BLAST, (2) short DNA sequences inserted into the pseudogene, (3) an ancestral intron sequence in duplicate pseudogenes, and (4) repetitive elements. These four scenarios can be distinguished by comparing the length of Gc and Gq and calculating the repetition content of the deviations between adjacent moves. Complexity in annotation of pseudogenes – insertion of one pseudogene into another.
A number of „nested” pseudogenes (green) were found in the ENm001 region, with protein homology (blue) supporting the annotation. This arrangement seems to have been generated by the insertion of a heterogeneous pseudogene (1) treated with nuclear ribonucleoprotein A1 (HNRPA1) into the genome on the negative strand. This was followed by a second insertion event in which a transcript derived from the mitochondrial genome was transposed into the pseudogeneic sequence HNRPA1. The order and orientation of the genes indicate that this mitochondria-derived sequence underwent additional rearrangement, including deletions, to leave a pseudogene NADH dehydrogenase 2 (MTND2) (2a) and a pseudogene NADH dehydrogenase 4 (MTND4) (2b) on the positive strand and a pseudogene of cytochrome B (CYTB) (2c) on the negative strand. A view of the protein alignment for the 5` end of the pseudogene HNRPA1 (in yellow) is clearly visible with a stop codon in the frame (indicated by *) and an image shift from +2 to +3 (highlighted by the red box). Drosophila-glutamate receptor. The term „pseudo-pseudogene” was coined for the gene encoding the ionotropic chemosensory glutamate receptor Ir75a of Drosophila sechellia, which carries a premature termination codon (PTC) and has therefore been classified as pseudogene. In vivo, the Locus D. However, Ir75a sechellia has a functional receptor due to translational reading of PTC.
The reading is detected only in neurons and depends on the nucleotide sequence downstream of the PTC. [24] This article is an overview of Pseudogene.org, a repository of detailed pseudogenic information compiled from various sources. Currently (as of June 2006) Pseudogene.org contains a compilation of pseudogenes which includes: The prevalence of pseudogenes in mammalian genomes is itself of considerable interest. This prevalence is generally believed to be related to increased LINE-mediated backtransposition activity (long intercalated elements) or other transposed elements (Brosius, 1991; Maestre et al., 1995; Esnault et al., 2000; Long et al., 2003; Marques et al., 2005; Wheelan et al., 2005; Pavlicek et al., 2006). Our first multispecific study of orthologous sequences for human pseudogenes supports this hypothesis and shows that ∼80% of human-treated pseudogenes come from primate-specific retroposed sequences. This is consistent with previous studies suggesting that an outbreak of retrotransposition events occurred in primates ∼40–50 million years ago (Ohshima et al. 2003; Zhang et al., 2003). Many human backlaid genes have also emerged from these events (Marques et al. 2005).
Interestingly, the absence of mouse spellings has been used by two research groups as a criterion for assigning human-treated pseudogenes (Torrents et al. 2003; van Baren and Brent 2006). Using data generated by the ENCODE multi-species sequence analysis group and the variation group, we began to investigate several fundamental concepts regarding pseudogene evolution and conservation. In particular, we used orthologous genomic sequences from 28 mammalian or vertebrate species to characterize in detail sequence decay and preservation of pseudogenes in relation to their surrounding genomic material and protein-coding genes. siRNA. Some endogenous siRNAs appear to be derived from pseudogenes, and therefore some pseudogenes play a role in regulating protein-coding transcripts. [29] One of the many examples is psiPPM1K. Treatment of RNAs transcribed from psiPPM1K produces siRNAs that can suppress the most common type of liver cancer, hepatocellular carcinoma.
[30] This and many other research have generated considerable enthusiasm for the possibility of attacking pseudogenes with/as therapeutics. [31] In this thesis, we describe our tested algorithm for the identification of pseudogenes (Zhang et al., 2004, 2003). The definition of pseudogene is somewhat ambiguous, as it is more difficult to confirm non-functionality than to confirm functionality. Our method has been developed and better used to detect pseudogenes that cannot be translated into proteins. The algorithm was implemented in a standalone software, `PseudoPipe`. (A) Schematic representations of the overlap between BLAST impacts and functional genes. The green rectangles represent the annotated gene exons and the red rectangles represent the BLAST moves. We expect some of the BLAST results to identify the proteins` parent genes or their homologs. Given the position of the exons of these genes, we eliminate all overlapping BLAST hits, as shown here. (B) Separation of BLAST blows into disjoint sentences based on query and position on chromosome.
Three disjoint sets are shown that correspond to different query proteins A, B and C. The first two disjoint sets represent the same region on the chromosome, they were both retained in this step. Overlapping BLAST moves in each disjoint set are filtered and removed. (C) Merging adjacent results. The BLAST hits in each disjointed set are first merged into „superhits”. The distance between adjacent superhits Gc is compared to the distance on the query protein Gq; adjacent superhits are fused when it is discovered that they are part of the same ancestral pseudogenetic structure and that the Gc gap is not too large. Processed pseudogenes often pose a problem for gene prediction programs and are often mistakenly identified as true genes or exons. It has been suggested that the identification of treated pseudogenes could help improve the accuracy of gene prediction methods. [2] Untreated (or duplicated) pseudogenes. Gene duplication is another common and important process in genome evolution. A copy of a functional gene can occur as a result of a gene duplication event caused by homologous recombination, such as the repetition of sinus sequences on misaligned chromosomes, and subsequently acquire mutations that result in the loss of copy function of the original gene. Duplicated pseudogenes generally have the same properties as genes, including intact exon-intron structure and regulatory sequences.
The loss of functionality of a duplicated gene generally has little effect on the ability of an organism, since an intact functional copy still exists. According to some evolutionary models, common duplicate pseudogenes indicate the evolutionary relationship between humans and other primates. [14] If pseudogenization is due to gene duplication, it usually occurs within the first million years after gene duplication, unless the gene has been subjected to selection pressure. [15] Gene duplication creates functional redundancy and it is generally not advantageous to carry two identical genes.