Contractions and expansions in gene size and number - Human Gene Evolution - page 329

lineages (McEvoy and Maeda, 1988; see Chapter 6, section 6.2.6). Finally, although
there are two semenogelin genes ( SEMG1 , SEMG2 ; 20q12-q13.1) in humans and
most Old World and New World monkeys, the Semg2 gene has been deleted from
the genome of the cotton-top tamarin ( Saguinus oedipus ) (Lundwall, 1998). There is
no evidence for any selective advantage resulting from any of these gene deletions.
In all cases cited, a similar paralogous gene was available to substitute for the
deleted locus. This genetic redundancy probably ensured that, owing to the absence
of purifying selection, such deletions came to be fixed through genetic drift.

8.1.2 Gross deletional polymorphisms

Gross gene deletions in two distinct glutathione S-transferase genes have been
found to occur as polymorphic variants in various human populations. In humans,
four gene families of glutathione S-transferases encode a series of enzymes respon-
sible for the metabolism of a wide range of xenobiotics (DeJong et al ., 1991; Pearson
et al ., 1993). The gene for the mu-class glutathione S-transferase ( GSTM1 ; 1p13.3)
is absent from between 10% and 64% of individuals depending upon the population
under study (Board et al ., 1990; Nelson et al ., 1995; Seidegard et al ., 1988). Loss of
the GSTM1 gene is due to a 15 kb deletion probably brought about by homologous
unequal recombination between two almost identical 4.2 kb repeats that flank the
GSTM1 gene ( Figure 8.1 ; Xu et al ., 1998). These repeats are likely to have originated
with the original duplication that gave rise to the mu-class glutathione S-transferase
genes more than 20 Myrs ago (Xu et al ., 1998). A similar deletional polymorphism
also occurs in the theta-class glutathione S-transferase ( GSTT1 ; 22q11.2) gene; the
gene is absent in ~38% of the Caucasian population (Brockmoller et al ., 1992;
Pemble et al ., 1994). Since the GSTM1 and GSTT1 genes are involved in xenobiotic
metabolism, it is quite possible that the presence/absence of these polymorphic
alleles are not selectively neutral (Weber, 1997).
Dichromacy (color blindness) is very common (occurring at a polymorphic fre-
quency (5-8%) in Caucasian males) with individuals so affected having either a dele-
tion of the green color pigment ( GCP ) gene or possessing a hybrid red/green color
pigment ( RCP / GCP ) gene in its place (Deeb et al ., 1995). Further variable gene
number polymorphisms, which probably also arose by homologous unequal recom-
bination, are apparent in the human -amylase gene cluster at chromosome 1p21

(Groot et al ., 1989) and the pepsinogen A gene cluster at 11q13 (Taggart et al ., 1987).

GSTM4 GSTM2 GSTM1 GSTM5

5.0 1.8 3.5 5.0 5.2

Eco RI
Hind III

13.6 5.2 11.4

10.3

GSTM4 GSTM2 GSTM5

5.0 5.2

Eco RI
Hind III 13.6 5.2 7.4

Figure 8.1. Model for homologous recombination between 4.2 kb repeats (open boxes)
flanking the human mu-class glutathione S-transferase ( GSTM1 ) gene leading to gene
deletion (Xu et al ., 1998). The GSTM1, GSTM2, GSTM4 and GSTM5 genes are
represented by solid bars. Vertical lines denote EcoR I and Hind III restriction sites. The
sizes of the EcoR I/ Hind III fragments are shown.