Pseudogenes and their formation - Human Gene Evolution - page 280

C822 and del G904) were found in the human -1,3 GT ( GGTA1 ) 'gene', located

at chromosome 9q34 (Larsen et al ., 1990). Since chimpanzees possess both dele-
tions whereas orangutan and gorilla only have del904, it was reasoned that del904
was the original inactivating mutation (Galili and Swanson, 1991). Old World
monkeys were found not to possess either lesion and no other inactivating muta-
tion was obvious. Clearly, as with urate oxidase, at least two distinct inactivating
mutations have occurred in apes and Old World monkeys. Selective pressure to
suppress

-galactosyl transferase expression may have been mediated by a
pathogen which infected primates via cell surface receptors containing the

-galacto-
syl epitopes and an effective host immune response would have required the sup-
pression of autologous

-galactosyl epitope. Alternatively, the pathogen might have expressed

-galactosyl epitope synthesis.

6.2.3 Elastase I gene

The human pancreatic elastase I ( ELA1 ; 12q13) 'gene' is transcriptionally silent
even though the coding sequence and splice junctions appear to be intact. Studies
of the corresponding (transcriptionally active) rat gene have demonstrated that
some 205 bp immediately upstream of the transcriptional start site are required
for pancreatic expression. This regulatory region comprises an enhancer between
-205 and -72 that contains all the information necessary for tissue-specific
expression, and a minimal promoter element between 71 and +8. The enhancer

contains three functional elements (A, B, and C), two of which (A and B) bind
pancreas-specific transcription factors (PTF1 and PDX1) that mediate the cell
type specificity of the enhancer. The 5

flanking region of the human ELA1 'gene'
was studied by Rose and MacDonald (1997). Its nucleotide sequence differs by
28% from its rat counterpart whilst its enhancer/promoter strength (as measured
by reporter gene assays) was 2.6% that of the homologous rat sequence.
Comparison of the rat and human gene 5

flanking regions revealed a total of 13
nucleotide differences within the A, B, and C elements. A combination of the
three human enhancer elements, 'repaired' by reference to the rat sequence,
together with the rat promoter, partially restored the activity of the human
enhancer (Rose and MacDonald, 1997). These authors went on to demonstrate
that two mutations in the A element and four mutations in the B element served
to abolish the binding of the cognate transcription factors. The degree to which
these lesions individually exert a deleterious effect on enhancer function will not
be apparent without further functional studies. In addition, without phylogenetic
studies of the ELA1 genes from other mammals/primates, it is unclear in which
order these mutations occurred during evolution. This notwithstanding, we may
still conclude that the silencing of the human ELA1 'gene' has come about
through the mutational inactivation of the upstream enhancer rather than
through the alteration of the coding region.

6.2.4 L -gulono- -lactone oxidase gene

Primates (including humans) and guinea pigs have at least one thing in common:
they are, unlike other mammals, unable to synthesize L -ascorbic acid from