Pseudogene Evolution in the Human Genome

Pseudogenes are those regions in the genome that have sequence similarity to functional genes but have decayed and do not have obvious functions. It is estimated that the human genome contain more than 10 000 easily recognizable pseudogenes and many more fragmented sequences, mainly arose through one of the following three mechanisms: duplication, retrotranposition and spontaneous loss of function.

Keywords: pseudogene; human genome; retrotransposition; evolution; comparative genomics

Figure 1. Sequence conservation of human retrotransposed pseudogenes. (a) Sequence completeness among human retrotransposed pseudogenes. Sequence completeness is defined as the ratio between the length of the predicted protein sequence from the pseudogene and the length of the corresponding functional gene. (b) Distribution of the nucleotide sequence identity between the retrotransposed pseudogenes and the corresponding functional genes (coding region only). (c) Distribution of the number of frame disruptions among retrotransposed pseudogenes. Pseudogenes that have the same number of frame disruptions were grouped together and the numbers of frame disruptions (x-axis) were plotted versus the size of the group (y-axis). The y-axis is on log scale. Reproduced from Zhang et al. (2003), with permission from Cold Spring Harbor Laboratory Press.
Figure 2. Phylogenetic tree of the human cyc pseudogenes. The tree is constructed using neighbour-joining technique on the protein-coding regions, and rooted by the fruitfly FLY_DC4 gene sequence. The tree included 49 human cyc pseudogenes and functional cyc genes from mouse, rat and chicken (see figure inset). Percentage bootstrap values (based on 1000 replications) supporting each node are also indicated. Reproduced from Zhang and Gerstein (2003) with permission from Elsevier.
Figure 3. The age distribution of human retrotransposed pseudogenes and repeats. Pseudogenes and repeats are grouped according to their sequence divergence from the present-day functional genes or inferred consensus sequence of the ancient repeats. The sequence divergence values were calculated following the Kimura 2-parameter model. The divergence data of the repeats were derived from the program RepeatMasker. A 1% sequence divergence represents 4.5 Myr in human. The shaded area represents the evolutionary time when the ancestral primates emerged. Reproduced from Zhang et al. (2003), with permission from Cold Spring Harbor Laboratory Press.
Figure 4. Evolutionary profile of human pseudogenes. Preservation of human genomic components in other species. The number of human pseudogenes (or genes) with orthologous sequences in individual species was computed and then plotted (by normalization with the total number in human) against each species. Data were derived from multispecies sequence alignment constructed by the ENCODE project. Reproduced from Figure 4 in Zheng et al. (2007), with permission from Cold Spring Harbor Laboratory Press.
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    Goncalves I, Duret L and Mouchiroud D (2000) Nature and structure of human genes that generate retropseudogenes. Genome Research 10: 672–678.
    Mighell AJ, Smith NR, Robinson PA and Markham AF (2000) Vertebrate pseudogenes. FEBS Letters 468: 109–114.
    Pavlicek A, Gentles AJ, Paces J, Paces V and Jurka J (2006) Retroposition of processed pseudogenes: the impact of RNA stability and translational control. Trends in Genetics 22: 69–73.
    Zhang Z and Gerstein M (2004) Large-scale analysis of pseudogenes in the human genome. Current Opinion in Genetics & Development 14: 328–335.
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Zhang, Zhaolei, and Zheng, Deyou(May 2008) Pseudogene Evolution in the Human Genome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020836]