Pseudogenes and their formation - Human Gene Evolution - page 264

6

Pseudogenes and their
formation

6.1 Pseudogene formation

Pseudogenes may be regarded as 'floating hulks,' gene-derived DNA sequences
that are no longer capable of being expressed as protein products. Some are the
remnants of once active genes that have acquired inactivating mutations which
either preclude their transcription or at the very least prevent mRNA translation.
Others are retrotransposed copies of expressed mRNAs which, since they almost
always lack promoter sequences, are incapable of being expressed and therefore
also tend to accumulate deleterious mutations. Pseudogenes ought not, however,
to be regarded entirely as evolutionary cul-de-sacs . Although it is unlikely that
reactivating (reverse) mutations will occur so as to restore their function, pseudo-
genes may nevertheless influence the evolution of other functionally significant
sequences by for example mediating recombination events (Beck et al ., 1996;
Takahashi et al ., 1982) or acting as sequence donors in gene conversion (Section
6.1.6).

6.1.1 The generation of pseudogenes by duplication

A considerable number of pseudogenes have been described in the human
genome that have retained the exon-intron structure of their functional source
genes ( Figure 6.1 ). A selection of the known pseudogenes of this type is presented
in Table 6.1 . One assumes that such sequences arose by simple duplication of func-
tional gene sequences but became inactivated since their intrinsic redundancy
prevented selection from maintaining their potential to be expressed (Wilde,
1985). Many of the examples listed in Table 6.1 have therefore accumulated non-
sense mutations, frameshift deletions and insertions, or single base-pair substitu-
tions within splice sites, any one of which would have been sufficient to render
the expression of the sequences impossible. Perhaps the archetypal example is
that of the human pseudogene ( CYP21P ) for cytochrome P450c21 which is
closely linked to its cognate gene ( CYP21 ; 6p21.3) as a result of a duplication
event which occurred before the separation of apes from Old World monkeys >23