Biology Reference
In-Depth Information
(a)
(b)
(c)
MAOA
MAOA
XRA
OATL1
TIMP1
SYN1
ARAF1
UBE1
UBE1
Inversion
ARAF1
SYN1
TIMP1
OATL1
GATA1
GATA1
XCR
ALAS2
ALAS2
Figure 2.8.
(a) Evolutionary origins of the human X chromosome. XCR, conserved region
of the X. XRA, recently added region. (b) Details of original gene order at the fusion
point. (c) Possible inversion event that placed the XCR genes,
UBE1
and
ARAF1
,
between the XRA genes,
SYN1
and
MAOA
(redrawn from Wilcox
et al.
, 1996).
The sex chromosomes however vary dramatically in terms of their evolu-
tionary conservation. The Y chromosome has undergone significant changes
during mammalian evolution (Glaser
et al
., 1998). By contrast, the X chromo-
some exhibits conservation of synteny between human and mouse (Ohno's
Law; Ohno, 1967). This is considered to be a consequence of X inactivation
because X-autosome translocations would have tended to be disadvantageous
by virtue of their interference with the dosage compensation mechanism.
Despite this, gene order on the X chromosome has changed significantly
between mouse and human with numerous inversions altering the relative
position of genes (Bardoni
et al
., 1991).
The human Y chromosome contains a number of active genes (Lahn and Page
1997; Vogt
et al
., 1997). Most notably it hosts the rapidly evolving sex determin-
ing gene,
SRY
(Yp11.3; Pamilo and O'Neil 1997; Whitfield
et al
., 1993) which
occurs in the sex chromosome-specific region, about 5 kb from its boundary with
the major PAR. In human, a few X-linked genes have functional homologues on
the Y chromosome (e.g.
CSF2RA
(Xp22.32, Yp11.3),
MIC2
(Xp22.33, Yp11.3),
RPS4X
(Xq13.1) and
RPS4Y
(Yp11.3),
ZFX
(Xp21.3-p22.1) and
ZFY
(Yp11.3),
AMELX
(Xp22.1-p22.31) and
AMELY
(Yp11.2)). Some Y chromosome homo-
logues are however nonfunctional, for example the
KAL1
pseudogene on Yq11.2
(Incerti
et al
., 1992) or the
XG
pseudogene on Yq11.21 (Weller
et al
., 1995). One
consequence of the sequence identity of the PARs between the sex chromosomes
is that the X chromosomal homologues escape X inactivation in females thereby
ensuring that gene dosage is maintained at the level found in males.
Genes identified in the nonrecombining portion of the Y chromosome (NRY)
appear to fall into two distinct classes (Lahn and Page, 1997):
