Frequent emergence and functional resurrection of processed pseudogenes in the human and mouse genomes.
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.
- SourceAvailable from: Craig Emory NelsonComparative Genomics, International Workshop, RECOMB-CG 2008, Paris, France, October 13-15, 2008. Proceedings; 01/2008
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ABSTRACT: In primates and other animals reverse transcription of mRNA followed by genomic integration creates retroduplications. Expressed retroduplications are either 'retrogenes' coding for functioning proteins or expressed 'processed pseudogenes', which can function as noncoding RNAs. To date, little is known about the variation in retroduplications in terms of their presence or absence across individuals in the human population. We developed new methodologies allowing us to identify 'novel' retroduplications (i.e., those not present in the reference genome), to find their insertion points, and to genotype them. Using these methods, we catalogued and analyzed 174 retroduplication variants in almost one thousand humans, which were sequenced as part of Phase 1 of the 1000 Genomes Project. The accuracy of our dataset was corroborated by (i) multiple lines of sequencing evidence for retroduplication (e.g., depth of coverage in exons vs. introns), (ii) experimental validation, and (iii) the fact that we can reconstruct a correct phylogenetic tree of human sub-populations based solely on retroduplications. We also show that parent genes of retroduplication variants tend to be expressed at the M-to-G1 transition in the cell cycle, and that M-to-G1 expressed genes have more copies of fixed retroduplications than genes expressed at other times. These findings suggest that cell division is coupled to retrotransposition and perhaps, is even a requirement for it.Genome Research 09/2013; · 14.40 Impact Factor