Pseudogenes and their formation - Human Gene Evolution - page 274

6.1.3 The generation of pseudogenes by other means

Although the vast majority of known pseudogenes are either inactivated genomic
copies (partial or complete) of functional genes or processed pseudogenes, there
are a few unusual examples which do not fit easily into either of these two group-
ings. One such case is that of the hybrid

-globin pseudogene found in lemurs
(Jeffreys et al ., 1982). The first and second exons plus intron 1 appear to be derived
from the

-

-globin pseudogene whilst intron 2, exon 3, and the 3 UTR origi-

nated from the -globin gene. The hybrid pseudogene probably originated from

an unequal crossover which fused sequences derived from the -globin pseudo-

gene and the -globin gene.

The cadherin pseudogene on human chromosome 5q13 described by Selig et al .
(1995) is also unusual. It contains one exon derived from the source gene encod-
ing cadherin 12 ( CDH12 ; 5p13-p14) plus flanking introns, an open reading frame
of 794 amino acids, and is transcribed at a 10-fold higher rate than the source
gene. Selig et al . (1995) proposed that this pseudogene had been only partially
processed in so far as the intron sequences had not been completely removed from
the mRNA before reverse transcription and integration had taken place. Other
examples of semi-processed human pseudogenes include one at 1q24-q25 derived
from the MADS box transcription factor 2 ( MEF2A ; 5q26) gene (Suzuki et al .,
1996) and another at 19q13.3-qter derived from the mitochondrial NADH:
ubiquinone oxidoreductase ( NDUFV2 ; 18p11.2-p11.31) gene (de Coo et al ., 1995)
and at least 13 pseudogenes which have independently originated from an identi-
cal mis-spliced transcript of the protein geranylgeranyltransferase type I

( PGGT1B ) gene (Dhawan et al ., 1998).

6.1.4 Origin and age of pseudogenes

Some indication of the relative age of a pseudogene can be obtained by the extent
of homology between the pseudogene and its parent or source gene. Thus, in the
human

-globin gene cluster on chromosome 16, the -globin pseudogene is

>99.5% homologous to its parental -globin ( HBZ ; 16p13.3-pter) gene whereas

the rather older -globin pseudogene is only 75-80% homologous to its parental

-globin ( HBA1 ; 16p13.3-pter) gene.
The approximate age of a pseudogene can be estimated by determining whether
or not an orthologous sequence is present at an identical location in other related
species of known phylogeny. Thus, the XG blood group pseudogene is present in
the great apes but not in Old World monkeys, New World monkeys or prosimians
(Weller et al ., 1995) whilst multiple copies of the keratinocyte growth factor
pseudogene are present in chimpanzee, gorilla but not in gibbons or Old World
monkeys (Kelley et al ., 1992). Similarly, the

1-globin pseudogene has been
found in prosimians and New World monkeys as well as the anthropoid apes and
human and is therefore thought to have originated very early in primate evolution
(Harris et al ., 1984). Rouquier et al . (1998) noted distinct human- and gorilla-
specific inactivating mutations in the olfactory receptor pseudogene (termed
912-93) that is located on human chromosome 11q11-q12 and which exhibits
synteny in the hominoid primates (Rouquier et al ., 1998). Finally, the serine
hydroxymethyltransferase processed pseudogene, derived from the SHMT1 gene