Pseudogene Evolution in the Human Genome


Pseudogenes are those regions in a genome that have sequence similarity to functional genes but have decayed and have no obvious functions. It is estimated that the human genome contains more than 10 000 easily recognisable pseudogenes and many more fragmented sequences, that arose mainly through one of the following three mechanisms: duplication, retrotranposition and spontaneous loss of function. The majority of the human retrotransposed (i.e. processed) pseudogenes are primate specific, arising from a burst of retrotransposition activities approximately 45 Ma. Although most of the human pseudogenes are most likely too degenerated to perform a biological function, ∼20% of them exhibit evidence of transcriptional activity based on data from multiple genomic studies. Furthermore, a handful of pseudogene transcripts have been demonstrated experimentally to gain novel functions as noncoding ribonucleic acids (RNAs), indicating that pseudogenes could be a reservoir for evolution innovation.

Key Concepts:

  • Pseudogenes are prevalent in the human genome and other mammalian genomes.

  • Most human pseudogenes are from past retrotranspositions occurring before the split of primate from other lineages.

  • Pseudogenes are a good source of DNA sequences for studying genome evolution.

  • Most human pseudogenes are most likely ‘dead’ but many of them can be transcribed.

  • Some human pseudogenes have adopted functions as noncoding RNAs.

Keywords: pseudogene; human genome; retrotransposition; evolution; noncoding RNAs

Figure 1.

Sequence conservation of human retrotransposed pseudogenes. (a) Sequence completeness among human retrotransposed pseudogenes. Sequence completeness is defined as the ratio of 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 against the size of the group (y‐axis). The y‐axis is on log scale. Reproduced from Zhang et al. (), with permission from Cold Spring Harbour Laboratory Press. © Cold Spring Harbour 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 the 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 () with permission from Elsevier. © 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 two‐parameter model. The divergence data of the repeats were derived from the programme RepeatMasker. A 1% sequence divergence represents 4.5 Myr in humans. The shaded area represents the evolutionary time when the ancestral primates emerged. Reproduced from Zhang et al. (), with permission from Cold Spring Harbour Laboratory Press. © Cold Spring Harbour 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 normalisation 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. (), with permission from Cold Spring Harbour Laboratory Press. © Cold Spring Harbour Laboratory Press.



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Zhang Z and Gerstein M (2004) Large‐scale analysis of pseudogenes in the human genome. Current Opinion in Genetics and Development 14: 328–335.

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Zhang, Zhaolei, and Zheng, Deyou(Feb 2014) Pseudogene Evolution in the Human Genome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020836.pub2]