Frequent emergence and functional resurrection of processed pseudogenes in the human and mouse genomes

Japan Biological Information Research Center, Japan Biological Informatics Consortium, AIST Bio-IT Research Bldg 7F, 2-42 Aomi, Tokyo, Japan.
Gene (Impact Factor: 2.08). 04/2007; 389(2):196-203. DOI: 10.1016/j.gene.2006.11.007
Source: PubMed

ABSTRACT Despite the wide distribution of processed pseudogenes in mammalian genomes, such as those of human and mouse, relatively little is known about their roles in genomic evolution. While gene duplications are recognized as one of the major driving forces in genome evolution, processed pseudogenes, which are retrotransposed copies of mRNAs, have been regarded as junk or selfish DNA for a long time. In order to elucidate the quantitative and qualitative contribution of processed pseudogenes to the mammalian genome evolution, we attempted to detect processed pseudogenes by extensively mapping the mRNAs to both the human and mouse genomes, and then we estimated the rate of their emergence. As a result, we revealed that the rate of pseudogene emergence was about 1-2% per gene per million years, which was as high as the rate (0.9%) of gene duplication in the human genome, although the rate of pseudogene emergence was found to drastically decrease in the hominid lineage. Furthermore, 1% of the processed pseudogenes seemed to be reinvigorated by post-retrotransposition transcription, many of them preserving the intact coding regions. Since the expression patterns of transcribed pseudogenes in various tissues were quite different between human and mouse, their emergence might have led to species-specific evolution. Our results indicate that the generation of processed pseudogenes was not wholly futile but instead has been an indispensable resource, driving dynamic evolution of the mammalian genomes.

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    • "Hence, they became evolutionary vestiges providing considerable information on genome history and evolution. A thorough analysis of the machinery of pseudogenization is relevant for estimating the frequency of duplicate genes in genomes (Sakai et al. 2007). "
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    ABSTRACT: Pseudogenes are defined as non-functional relatives of genes whose protein-coding abilities are lost and are no longer expressed within cells. They are an outcome of accumulation of mutations within a gene whose end product is not essential for survival. Proper investigation of the procedure of pseudogenization is relevant for estimating occurrence of duplications in genomes. Frankineae houses an interesting group of microorganisms, carving a niche in the microbial world. This study was undertaken with the objective of determining the abundance of pseudogenes, understanding strength of purifying selection, investigating evidence of pseudogene expression, and analysing their molecular nature, their origin, evolution and deterioration patterns amongst domain families. Investigation revealed the occurrence of 956 core pFAM families sharing common characteristics indicating co-evolution. WD40, Rve_3, DDE_Tnp_IS240 and phage integrase core domains are larger families, having more pseudogenes, signifying a probability of harmful foreign genes being disabled within transposable elements. High selective pressure depicted that gene families rapidly duplicating and evolving undoubtedly facilitated creation of a number of pseudogenes in Frankineae. Codon usage analysis between protein-coding genes and pseudogenes indicated a wide degree of variation with respect to different factors. Moreover, the majority of pseudogenes were under the effect of purifying selection. Frankineae pseudogenes were under stronger selective constraints, indicating that they were functional for a very long time and became pseudogenes abruptly. The origin and deterioration of pseudogenes has been attributed to selection and mutational pressure acting upon sequences for adapting to stressed soil environments.
    Journal of Biosciences 11/2013; 38(4):727-32. DOI:10.1007/s12038-013-9356-1 · 1.94 Impact Factor
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    • "MBE " dead on arrival. " However, as a number of studies shows, many of them do acquire new functions (Burki and Kaessmann 2004; Krasnov et al. 2005; Sakai et al. 2007; Kaessmann et al. 2009). These new functions, usually different from the functions of parental genes, may come from the gain of new spatiotemporal expression patterns, imposed by the content of the genomic sequence surrounding inserted cDNA. "
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    ABSTRACT: Gene duplicates generated via retroposition were long thought to be pseudogenized and consequently decayed. However, a significant number of these genes escaped their evolutionary destiny and evolved into functional genes. Despite multiple studies, the number of functional retrogenes in human and other genomes remains unclear. We performed a comparative analysis of human, chicken, and worm genomes in order to identify "orphan" retrogenes, i.e. retrogenes that have replaced their progenitors. We located twenty five such candidates in the human genome. All of these genes were previously known and majority has been intensively studied. Despite this, they were never been recognized as retrogenes. Analysis revealed that the phenomenon of replacing parental genes by their retrocopies has been taking place over the entire span of animal evolution. This process was often species-specific and contributed to interspecies differences. Surprisingly, these retrogenes, which should evolve in a more relaxed mode, are subject to a very strong purifying selection, which is on average, two and a half times stronger than other human genes. Also, for retrogenes, they do not show a typical overall tendency for a testis specific expression. Notably, seven of them are associated with human diseases. Recognizing them as "orphan" retrocopies, which have different regulatory machinery than their parents, is important for any disease studies in model organisms, especially when discoveries made in one species are transferred to humans.
    Molecular Biology and Evolution 10/2012; 30(2). DOI:10.1093/molbev/mss235 · 14.31 Impact Factor
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    • "Recently , several intriguing examples of primate retrogenes have been reported. For example, the human brain-specific isotype of the glutamate dehydrogenase (GLUD2) gene (Burki and Kaessmann 2004) and the brain-and testisspecific CDC14Bretro gene, which has evolved from the CDC14B cell cycle gene (Rosso et al. 2008), emerged by retroposition in a hominoid ancestor (Harrison et al. 2005; Marques et al. 2005; Vinckenbosch et al. 2006; Sakai et al. 2007; Baertsch et al. 2008; Kojima and Okada 2009). "
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