Pseudogenes and their formation - Human Gene Evolution - page 269

pseudogene which has no such lesions and retains an open reading frame (Karin
and Richards, 1982). This sequence is nevertheless probably not transcribed
since, owing to its mRNA origin, it necessarily lacks the promoter elements nec-
essary for transcription to occur. In general, retrotransposed pseudogenes are
rarely associated with active promoter elements and are not therefore usually
expressed. Again there are always exceptions, for example the human glutamine
synthetase pseudogene which contains a functional promoter/enhancer in its 5 ′

flanking sequence that allows it to be transcribed although not expressed (owing
to the presence of numerous frameshift mutations) (Chakrabarti et al ., 1995).
Those processed 'pseudogenes' which possess both open reading frames and some
inherent or acquired promoter activity such that they can be expressed, are really
not pseudogenes at all but rather examples of gene creation by retrotransposition,
a topic covered in Chapter 9, section 9.6.
To have been inherited, processed pseudogenes must have originated in the
germline. It therefore follows that their functional source genes must have been
expressed in the germline. Consistent with this assumption, many processed
pseudogenes correspond either to ubiquitously expressed 'housekeeping' genes
(e.g. snRNA genes) or to genes that are known to be expressed in germ cells (e.g.

-tubulin; Lewis and Cowan, 1990) ( Table 6.2 ). However, some processed pseudo-
genes are derived from transcripts of tissue-specific genes such as those encoding
the immunoglobulins ( Table 6.2 ). These pseudogenes may have originated from
ectopic transcripts, the consequence of the 'leaky' transcription which appears to
be a property of every gene in every cell. In a very few cases, processed pseudo-
genes have been shown to be derived from antisense transcripts (Rozmahel et al .,
1997; Zhou et al ., 1992).

Table 6.2. Examples of human pseudogenes generated by retrotransposition

Pseudogene Chromosomal location/comments Reference

Dihydrofolate reductase Unlinked to functional source gene Chen et al . (1982)

(2) DHFR (5q11-q13) Shimada et al . (1983)

Anagnou et al . (1985)

ADP-ribosyltransferase, Chromosomes 13 and 14. Unlinked to Lyn et al . (1995)

NAD + (2) functional source gene ADPRT (1q42).

Present in gorilla (98% homologous).
Originated ~27 Myrs ago.

Ribosomal protein L7 Located within intron 1 of c- fms ( CSF1R ) Sapi et al . (1994)

gene (5q33)

High mobility group Flanked by 15 bp direct repeat. Stros and Dixon (1993)

protein Originated only ~1 Myrs ago.

Topoisomerase 1 Chromosome 1. Truncated. Unlinked to Zhou et al . (1992)

functional source gene TOP1 (20q12-q13)

Glutamine synthetase Flanked by 9 bp direct repeat. Chakrabarti et al . (1995)

Transcribed.

FAU proto-oncogene Chromosome 18. Integrated within Kas et al . (1995)

sequence homologous to promoter of
islet amyloid polypeptide ( IAPP ) gene. 317
amino acid open reading frame. Not
transcribed. Unlinked to FAU gene (11q13)