Biology Reference
In-Depth Information
9.1.5 Common sites for inversions in pathology and evolution?
It has been known for some time that chromosomal inversions in human pathol-
ogy are nonrandomly distributed although it remains unclear whether this is due
to interchromosomal differences or to bias of ascertainment (Dutrillaux
et al
.,
1986; Madan, 1995). Some of these inversions have nevertheless been character-
ized with sufficient precision to allow comparison with inversions that have
occurred in the karyotypic evolution of the hominids (Dutrillaux, 1988; Yunis
and Prakash, 1982). Miro
et al
. (1992) performed such a comparison and demon-
strated that 10/20 pericentric inversions and 1/4 paracentric inversions which had
occurred during human chromosome evolution coincided (albeit at low level res-
olution) with known sites of pathological inversion. These (evolutionary) inver-
sions were inv(1) (p12q21.22), inv(2) (p11.2q13), inv(4) (p14q21.1), inv(5)
(p13.3q13.3), inv(7) (q11.23q22.2), inv(8) (p21.1q22.1), inv(9) (p24.2q12), inv(11)
(p15.5q13), inv(16) (p11.2q12.1), inv(18) (p11.32q11.2), and inv(Y) (p11.2q11.23).
If the sites that have been involved in chromosome inversions during primate
evolution were also to be involved in cases of human chromosome pathology, this
would argue for certain chromosomal regions possessing sequence characteristics
(possibly long highly conserved inverted repeats) that could predispose to this
type of lesion. Thus higher resolution studies such as that on human chromosome
12q15 (which contains breakpoints associated with both benign solid tumors and
a pericentic inversion that occurred during hominoid evolution; Nickerson and
Nelson, 1997) could yield valuable insights into the mechanisms underlying chro-
mosome rearrangement in both pathology and evolution.
9.2 Translocations and transpositions
The human genome is replete with examples of the transposition and transloca-
tion of gene sequences during evolution. A selection of some of the most notable
examples are given here while others have been discussed in the context of gene
duplication (see Chapter 8, section 8.5). The occurrence of most translocations
has been inferred from the localization of evolutionarily related genes on different
chromosomes or different chromosomal arms. One example is provided by the
human aminoacyl-tRNA synthetase gene family (Brenner and Corrochano, 1996)
whose evolution is depicted in
Figure 9.2
. Another is the human
-aminobutyric
acid receptor (GABA
A
R) which comprises several different types of subunit that
combine to form a pentameric channel complex and which are encoded by a small
but dispersed gene family. The
GABRA1
,
GABRB2
and
GABRG2,
genes have
been localized to chromosome 5q34-q35 (Russek and Farb, 1994) whilst similar
clusters comprising
GABRA2
,
GABRB1,
and
GABRG1
(4p13-p12) and
GABRA5
,
GABRB3
and
GABRG3
(15q11.2-q12) are present on two other chro-
mosomes. This organization is compatible with the duplication of an ancestral
gene cluster and its translocation to other chromosomes.
Tryptophan hydoxylase, tyrosine hydroxylase and phenylalanine hydroxylase
are members of the family of pterin-dependent aromatic amino acid hydroxylases
and are encoded by the
TPH
(11p15.3-p14),
TH
(11p15.5) and
PAH
(12q22-q24.1)
genes, respectively.
PAH
and
TPH
are estimated to have arisen by a process of
