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( Pithecia irrorata ), the capuchin ( Cebus nigrivittatus ) and the tamarin ( Saguinus mys-
tax ) (Boissinot et al ., 1998; Shyue et al ., 1995).
Zhou et al . (1997) studied the X-linked opsin gene of two nocturnal prosimians,
the bushbaby species Galago senegalensis and Otolemur garnettii . At those amino
acid positions known to cause spectral differences, however, the cone pigment
possessed identical residues to those of the marmoset protein. This suggests that,
in spite of the bushbaby's nocturnal existence, its X-linked opsin gene is under
functional constraint. Consistent with this view, Zhou et al . (1997) noted two
amino acid substitutions which may be important for maximizing dim light sen-
sitivity.
The kringle domains of apolipoprotein(a). The human apolipoprotein(a)
( LPA ; 6q27) gene emerged from the plasminogen ( PLG ; 6q27) gene by a process
of gene duplication followed by intragenic amplification of exons within the LPA
gene (Chapter 8, section 8.6). Apolipoprotein(a) is a component of the cholesteryl
ester-rich particle lipoprotein(a) within which it is covalently linked to
apolipoprotein B100. Lipoprotein(a) has been postulated to play a role in fibri-
nolysis by competing with plasminogen for binding to fibrin, thereby interfering
with clot lysis. Fibrin binding appears to be potentiated by lysine-binding sites in
some of the many kringle domains of apolipoprotein(a). Kringle IV-10 of human
apolipoprotein(a) most closely resembles that of plasminogen kringle IV and
appears to be critical for the fibrin-binding potential of lipoprotein(a). The lysine-
binding sites of apolipoprotein(a) consist of a hydrophobic trough containing
three aromatic amino acids (Trp62, Phe64, and Trp72), an anionic centre com-
posed of two aspartic acid residues (Asp55 and Asp57), and a cationic centre com-
prising two residues, Lys35 and Arg71. Kringles IV-1, IV-2, IV-3, and IV-4 of
apolipoprotein(a) do not bind to lysine and in each case, this is associated with the
absence of Asp57 within the kringle. Two different substitutions in kringle IV-10
have occurred during primate evolution which are associated with the loss of the
lysine-binding properties of the lipoprotein(a) particle; a Trp72
Arg substitu-
tion in rhesus monkey (Scanu et al. , 1993; Tomlinson et al., 1989) and an
Asp57
Asn substitution in chimpanzee (Chenivesse et al. , 1998). The physiolog-
ical consequences of these two substitutions are however as yet unknown.
The DNA-binding specificity of steroid receptors. Gene regulation by steroid
hormones is mediated by binding of the hormone ligand to its cognate receptor
(Chapter 4, section 4.2.3, Nuclear receptor genes ). Upon ligand binding, most nuclear
receptors then interact as dimers with their response elements, each monomer
binding to a half-site sequence. These response elements comprise two 6 bp half-
site sequences organized as palindromic repeats with 3-5 bp separating the half
sites. Thus the thyroid hormone, retinoic acid and estrogen receptors recognize
the half-site sequence TGACCT whereas the androgen, progesterone and gluco-
corticoid receptors recognize the half-site sequence TGTTCT. More specifically,
the consensus estrogen response element (ERE) is AGGTCANNNTGACCT
whilst the consensus glucocorticoid response element (GRE) is GGTACANNNT-
GTTCT (Zilliacus et al. , 1995). These response elements exhibit a 3 bp spacer
between half-sites. By contrast, the thyroid hormone receptor recognizes a 4 bp
 
 
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