Pseudogenes and their formation - Human Gene Evolution - page 273

of the source gene which will determine both the efficiency of priming of reverse
transcriptase and of their eventual integration of reverse transcripts. Thus, for
example, the plethora of U3 snRNA pseudogenes may be explicable in terms of
the inherent ability of U3 snRNA to act as a self-priming template for reverse
transcriptase (Bernstein et al ., 1983). Both human and murine cells possess an
endogenous reverse transcriptase activity (Maestre et al ., 1995; Tchenio et al .,
1993) although it is unclear whether this is derived from retroviral infection
(Carlton et al ., 1995), endogenous sources of reverse transcriptase such as retrovi-
ral elements (Chapter 1, section 1.4.4) or, perhaps more likely, LINE elements
(Dhellin et al ., 1997; Jurka, 1997; Chapter 1, section 1.4.3).
Some human processed pseudogenes have been inserted into the introns of
other genes, for example a ribosomal protein L7 pseudogene in intron 1 of the
c- fms ( CSF1R ; 5q33) proto-oncogene (Sapi et al ., 1994), a phosphoglycerate
mutase pseudogene in intron 1 of the Menkes disease ( ATP7A ; Xq13.3) gene
(Dierick et al ., 1997), an L5 ribosomal protein pseudogene in an intron of the
small nuclear ribonucleoprotein N ( SNRPN ; 15q12) gene (Buiting et al ., 1996), an
L21 ribosomal protein pseudogene in intron 13 of the breast cancer ( BRCA1 ;
17q21) gene (Smith et al ., 1996) and an adenylate kinase 3 pseudogene in intron 10
of the neurofibromatosis type 1 ( NF1 ; 17q11.2) gene (Xu et al ., 1992). If integrated
upstream of a gene, the pseudogene sequence may affect expression of that gene.
For instance, a processed ribosomal protein S25 pseudogene, which has become
integrated into the promoter region of a rat class I alcohol dehydrogenase gene,
inactivated a glucocorticoid response element and contributed a novel suppressor
element (Cortese et al ., 1994). Similarly, the human L38 ribosomal protein
processed pseudogene has become integrated into the promoter of the type-1
angiotensin II receptor ( AGTR1 ; 3q21-q25) gene although the effect, if any, on
the expression of the gene is unclear (Espinosa et al ., 1997). In general, the sites
into which processed pseudogenes integrate appear to be AT-rich and various
models have been proposed which attempt to describe the process of integration
(Vanin, 1984; Wilde, 1985). Co-retrotransposition sometimes occurs with other
sequences e.g. endogenous retroviral elements (Lyn et al ., 1995), LINE elements
(Rozmahel et al ., 1997) and possibly Alu sequences (Koller et al ., 1991).
Some pseudogenes may be duplicated copies of pre-existing processed pseudo-
genes, for example the tandemly arranged proliferating cell nuclear antigen
pseudogenes on chromosome 4q34 (Taniguchi et al ., 1996), the L7a ribosomal pro-
tein pseudogenes associated with the closely linked lymphotactin ( LTNA ) and

( LTNB ) genes on chromosome 1q23 (Yoshida et al ., 1996) or the elk-1 pseudo-
gene associated with the immunoglobulin heavy chain locus ( IGHV ) on 14q32
(Harindrath et al ., 1998).
A highly unusual presence/absence polymorphism has been noted for a human
dihydrofolate reductase processed pseudogene (Anagnou et al. , 1984). This
pseudogene is present in only a proportion of individuals and this proportion
varies between racial groups. However, it is unclear whether the polymorphism is
a consequence of the recent acquisition of the pseudogene or whether it instead
results from its occasional loss.