Contractions and expansions in gene size and number - Human Gene Evolution - page 359

mutable and therefore most informative of human microsatellites that have been
selected as genetic markers (Ellegren et al ., 1995). In principle, the large size of the
human population could have compounded this effect since it could support a
higher level of genetic diversity; in smaller populations, much variability is lost as
alleles go to fixation. In practice, however, it would appear as if ascertainment bias
cannot be the sole explanation for inter-specific differences in microsatellite repeat
length (Cooper et al ., 1998). Thus, the tendency for microsatellite loci to be longer
in humans may not simply be an experimental artefact.
8.8.3 Telomeric and centromeric repetitive DNA
Telomeric TTAGGG repeat number varies not only between human chromoso-
mal arms but also between individuals (Brown et al ., 1990; Martens et al ., 1998).
Indeed, there is some evidence in humans for the exchange of telomeric and sub-
telomeric repeats between nonhomologous chromosomal ends (van Deutekom et
al ., 1996). Since satellite DNA sequences at the telomeric junctions of chim-
panzees do not show any similarity to their counterparts in human or orangutan,
it is likely that telomeres became reorganized relatively recently during primate
evolution (Baird and Royle, 1997; Royle et al ., 1994; Royle, 1996).
Alphoid satellite DNA is found as a tandem repeat in long chromosome-spe-
cific arrays at the centromeres of all primate chromosomes (Warburton and
Willard, 1996). These arrays are highly variable within and between homologous
chromosomes in the same species.
8.9 Expansion of unstable repeat sequences
DNA sequences that are internally repetitive are particularly prone to misalign-
ment during DNA synthesis (Djian, 1998; Di Rienzo et al ., 1994; Levinson and
Gutman, 1987; Schlötterer and Tautz, 1992; Valdes et al ., 1993). If such misalign-
ment takes place, the nascent strand can slip back in multiples of the repeat unit
and the newly synthesized DNA strand will be elongated by comparison with the
parental strand. Since many coding sequences contain simple sequence repeats
(Tautz et al ., 1986) (for example, the genes encoding the 28S and 18S ribosomal
RNAs ( RNR1 - 5 ; Hancock, 1995a; Hancock and Dover, 1988) and the TATA-
binding protein TBP ( TBP ; Hancock, 1993)), repeat expansion may have been
involved in the evolution of these sequences (Hancock 1995b; see Section 8.9.2).
However, these simple repeats also have the potential to be involved in disease
pathogenesis (see Section 8.9.1) and it is from studies of genetic disease that most
of our knowledge of triplet repeat expansion is derived.
8.9.1 Triplet repeat expansion disorders
One manifestation of DNA slippage involving simple repetitive sequences is the
instability of certain trinucleotide repeat sequences (reviewed by Djian, 1998;
Monckton and Caskey, 1995; Richards and Sutherland, 1996; Sutherland and
Richards, 1995; Timchenko and Caskey, 1996; Wells, 1996). This mutational