Pseudogenes and their formation - Human Gene Evolution - page 279

by their clinical manifestations (assuming that they are not embryonic lethal) and
we should expect them to be rapidly removed from the population by natural
selection. On the other hand, the inactivation of a nonessential gene could in
principle have relatively few deleterious consequences and might even have a
beneficial effect under the appropriate circumstances. One possible example of
this is the C4b-binding protein -chain gene ( C4BPB ; 1q32) gene which occurs

as a single copy functional gene in the human genome but has been inactivated in
the mouse (Rodriguez de Cordoba et al ., 1994). That the loss of this gene has been
fixed evolutionarily in the murine lineage suggests that it is at least neutral with
respect to fitness. It's loss may even have conferred a selective advantage
(antithrombotic effect?) in which case, it could have become fixed within a rela-
tively short period of evolutionary time. Several similar examples of the inactiva-
tion of single copy genes from primate genomes have also been documented and
these single copy pseudogenes will now be described in some detail.

6.2.1 Urate oxidase gene

Urate oxidase is a copper binding enzyme found in most vertebrates which catal-
yses the conversion of uric acid to allantoin. Although found in Old World mon-
keys and in the majority of New World monkeys, urate oxidase activity has been
lost in the hominoid line. The human urate oxidase ( UOX ; 1p22) 'gene' was iso-
lated by screening a genomic library with a porcine cDNA probe (Wu et al ., 1989).
It was found to contain two nonsense (CGA TGA) mutations at codons 33 and

187 (Wu et al ., 1989; Yeldandi et al ., 1990). These lesions were also found to be pre-
sent in chimpanzee and gorilla but only the codon 33 mutation was detected in
orangutan (Yeldandi et al ., 1991). This implies that the codon 33 mutation was the
original inactivating mutation and that it must have occurred before the diver-
gence of orangutan from the chimpanzee/human line, between 7 Myrs and 13
Myrs ago. Urate oxidase activity is also absent in the gibbon but this has been
shown to be due to a 13 bp deletion in exon 2 of the Uox gene (Wu et al. , 1992). The
loss of urate oxidase activity in primates has therefore been due to the occurrence
of at least two distinct gene lesions in different lineages. That this gene could have
been lost in primates as a result of at least two independent mutational events is
consistent with its loss being advantageous. Although somewhat far-fetched per-
haps, it has been suggested that since uric acid is a potent antioxidant, an
increased uric acid concentration might have contributed to a lowering of the
somatic mutation rate with a consequent increase in hominoid lifespan. The loss
of urate oxidase may however be responsible for at least some cases of renal stones
and gouty arthritis in humans.

6.2.2 -1,3-Galactosyltransferase gene

-1,3-Galactosyltransferase ( -1,3 GT) is responsible for the synthesis of the

-galactosyl epitope present in the cell surface receptors of most mammals includ-
ing prosimians and New World monkeys. However, the catarrhines (Old World
monkeys, apes and humans) appear to lack this epitope and produce large
amounts of antibodies against it. Two inactivating single base-pair deletions (del