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the gene from which they originated. This may reflect mechanistic differences in
pseudogene generation.
Since many of the pseudogenes listed in Table 6.1 are duplicated copies of entire
genes that include their original promoters, it is not surprising that some are
capable of being transcribed. However, some of the partial, truncated pseudogenes
also appear to be transcribed. We may nevertheless assume that the nonsense
mutations and frameshift insertions and deletions acquired by these sequences
serve to preclude the translation of any mRNAs synthesized.
A particularly good example of the generation of multiple partial pseudogenes
is that of the numerous sequences related to the neurofibromatosis type 1 ( NF1 ;
17q11.2) gene identified on human chromosomes 2, 12, 14, 15, 18, 20, 21 and 22
(Gasparini et al ., 1993; Hulsebos et al ., 1996; Kehrer-Sawatzki et al ., 1997; Legius
et al ., 1992; Marchuk et al ., 1992; Purandare et al ., 1995; Suzuki et al ., 1994). These
NF1-homologous sequences contain numerous nucleotide substitutions, small
deletions and insertions (some inactivating) but still exhibit >90% homology to
the corresponding sequences of the NF1 gene. They appear to have arisen by par-
tial duplication of the NF1 gene between 22 Myrs and 33 Myrs ago with subse-
quent rounds of duplication generating new copies which were then transposed to
the pericentromeric regions of the other chromosomes (Régnier et al ., 1997).
In cases where the parental source gene is intronless [e.g. some argininosucci-
nate synthetase pseudogenes (Nomiyama et al ., 1986) and the dopamine D5 recep-
tor pseudogene (Marchese et al ., 1995)], the pseudogenes may have been
secondarily created by the genomic duplication of pre-existing processed pseudo-
genes (see Section 6.1.2 below).
The occasional human pseudogene manifests a presence/absence polymor-
phism, for example the T-cell receptor
v6.10 pseudogene which has been found
in the genome of most but not all individuals tested (Li et al ., 1993).
6.1.2 The generation of pseudogenes by retrotransposition
The second main category of pseudogenes probably accounts for the majority of
inactivated gene sequences found in the human genome. A selection of pseudo-
genes of this type is presented in Table 6.2 . They are termed processed pseudogenes
since they are thought to have originated by retrotransposition of a correctly
processed mRNA intermediate lacking intervening sequences (Vanin, 1984;
Weiner, 1986; Figure 6.1 ). The mRNA origin is evidenced by the lack of introns
and the frequent presence of poly(A) tracts at their 3
ends (Vanin, 1984).
Flanking direct repeats, commonly of 9-17 bp (Vanin, 1984), are usually present
and have probably been acquired during the process of integration. Many
processed pseudogenes correspond to the entire length of the coding region of
their source genes but others are truncated (e.g. CFTR exon 9 pseudogene frag-
ments; Rozmahel et al ., 1997). The vast majority of processed pseudogenes are
located on different chromosomes from their functional source genes ( Table 6.2 ).
This is not very surprising in view of the fact that retrotransposition necessarily
requires a mobile mRNA intermediate.
Many processed pseudogenes have, like their duplication-derived counterparts,
acquired multiple genetic lesions that preclude their expression. This is not how-
ever an invariant finding as evidenced by the human metallothionein processed
 
 
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