Processed Pseudogenes and Their Functional Resurrection in the Human and Mouse Genomes


The genomes of human and mouse contain thousands of pseudogenes. Processed pseudogenes, which were derived through retrotransposition, were recognized as ‘dead on arrival’ elements in the genomes, and they have been thought to have no contribution to genome evolution. However, several recent studies have shown that a significant portion of processed pseudogenes were transcribed and were able to function as noncoding ribonucleic acid (RNA) genes. Since the transcription mechanism and functions of transcribed processed pseudogenes still remain unknown, it is of great importance to elucidate the biological roles of processed pseudogenes by both approaches of experiments and bioinformatics.

Keywords: retrotransposition; retrotransposed copy; retrogene; processed pseudogene; transcription

Figure 1.

(a) Genomic structures of and sequence identities between Rho family members. NID stands for the nucleotide identity and AID for the amino acid identity. (b) Nucleotide alignment of the 5′‐flanking regions of the RHOB genes obtained from human, mouse and rat. The arrow indicates the transcription start site. Two cis‐elements for the transcription initiation are highlighted. Protein‐coding regions are underlined. The alignment was constructed by Clustal W (ver. 1.83).

Figure 2.

Classification of a retrotransposed copy into four categories: retrogene, putative processed pseudogene, transcribed processed pseudogene and processed pseudogene. Light grey boxes indicate exons of a functional gene and dark grey boxes indicate retrotransposed copies. The jagged arrows denote substitutions that collapse protein‐coding regions of retrotransposed copies.



Emerson JJ, Kaessmann H, Betran E and Long M (2004) Extensive gene traffic on the mammalian X chromosome. Science 303: 537–540.

Harrison PM, Zheng D, Zhang Z, Carriero N and Gerstein M (2005) Transcribed processed pseudogenes in the human genome: an intermediate form of expressed retrosequence lacking protein‐coding ability. Nucleic Acids Research 33: 2374–2383.

Hirotsune S, Yoshida N, Chen A et al. (2003) An expressed pseudogene regulates the messenger‐RNA stability of its homologous coding gene. Nature 423: 91–96.

Kaneko S, Aki I, Tsuda K et al. (2006) Origin and evolution of processed pseudogenes that stabilize functional Makorin1 mRNAs in mice, primates and other mammals. Genetics 172: 2421–2429.

Korneev SA, Park JH and O'Shea M (1999) Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene. Journal of Neuroscience 19: 7711–7720.

Ohshima K, Hattori M, Yada T et al. (2003) Whole‐genome screening indicates a possible burst of formation of processed pseudogenes and Alu repeats by particular L1 subfamilies in ancestral primates. Genome Biology 4: R74.

Sakai H, Koyanagi KO, Imanishi T, Itoh T and Gojobori T (2007) Frequent emergence and functional resurrection of processed pseudogenes in the human and mouse genomes. Gene 389: 196–203.

Torrents D, Suyama M, Zdobnov E and Bork P (2003) A genome‐wide survey of human pseudogenes. Genome Research 13: 2559–2567.

Zhang Z, Harrison PM, Liu Y and Gerstein M (2003) Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome. Genome Research 13: 2541–2558.

Zheng D, Frankish A, Baertsch R et al. (2007) Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and evolution. Genome Research 17: 839–851.

Further Reading

Esnault C, Maestre J and Heidmann T (2000) Human LINE retrotransposons generate processed pseudogenes. Nature Genetics 24: 363–367.

Mighell AJ, Smith NR, Robinson PA and Markham AF (2000) Vertebrate pseudogenes. FEBS Letters 468: 109–114.

Zheng D and Gerstein MB (2007) The ambiguous boundary between genes and pseudogenes: the dead rise up, or do they? Trends in Genetics 23: 219–224.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Sakai, Hiroaki, Itoh, Takeshi, and Gojobori, Takashi(Jul 2008) Processed Pseudogenes and Their Functional Resurrection in the Human and Mouse Genomes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021000]