Pseudogenes and their formation - Human Gene Evolution - page 281

D -glucose owing to a deficiency of the enzyme L -gulono- -lactone oxidase. Using

a rat cDNA as a probe, Nishikimi et al . (1994) isolated the once active human L -
gulono-

-lactone oxidase ( GULOP ) 'gene' which is located at chromosome
8p21.1. A considerable number of inactivating mutations were found including
the deletion of exon VIII, two 1 bp deletions, one 1 bp insertion and two nonsense
mutations. The presence of two non-consensus dinucleotides at donor splice sites
(GC and GG instead of GT) also suggested the introduction of potentially inacti-
vating mutations at splice sites. Since both Old World and New World monkeys
are deficient in L -gulono- -lactone oxidase whilst prosimians possess this

enzyme, its loss must have preceded the divergence of New World from Old
World monkeys (~45 Myrs ago) but occurred after the divergence of the prosimi-
ans from the simian line (50-65 Myrs ago).

6.2.5 ADP-ribosyltransferase 1 gene

ADP-ribosyltransferase 1 (RT6) is a glycosyl phosphatidylinositol-anchored cell
membrane protein expressed in peripheral T cells and intra-epithelial lympho-
cytes. In the rat, expression of RT6 has been used to distinguish subsets of T cells
and a defect in RT6 expression has been associated with susceptibility to autoim-
mune type I diabetes. Haag et al . (1994) have shown that the human ( ART2P ;
11p15) and chimpanzee 'genes' contain three nonsense mutations, at codons 47,
141, and 193 respectively, which serve to inactivate them. No further copies of the
ART2P 'gene' were detectable in the human genome consistent with its presumed
status of single copy pseudogene. It is possible that inactivation of the ART2P
gene conferred a selective advantage if, for example, it resulted in the loss of a
membrane receptor for a pathogenic virus. It is as yet unclear if loss of the RT6
protein confers increased susceptibility to disease.

6.2.6 Haptoglobin gene

Haptoglobin, a hemoglobin-binding protein, is encoded by three closely linked
genes in chimpanzee ( HP , HPR, and HPP ) but only two ( HP , HPR ; 16q22.1) in
human. The loss of the HPP 'gene' in human occurred after the separation of the
human and chimpanzee lineages by an unequal homologous crossover that
deleted most of the the HPP gene (McEvoy and Maeda, 1988).

6.2.7 Fertilin- gene

In most mammals including macaques and baboons, -fertilin contributes a sub-

unit to a heterodimeric membrane glycoprotein on the sperm surface. The
macaque and baboon possess two -fertilin genes which appear to lack introns

(indicative perhaps of a retrotranspositional origin). Only a single copy homo-
logue ( FTNA ) is present in the human genome and, although this sequence is
transcribed in the testis, it represents a nonfunctional pseudogene since it con-
tains numerous mutations which render translation of the transcript impossible
(Jury et al ., 1997). What is puzzling is that although the 5 half of the human

FTNA 'gene' is highly homologous to the macaque Ftna1 gene, the 3 half differs