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and Louis, 1998). Minisatellites frequently exhibit substantial allelic variability
with respect to repeat number (Jeffreys
et al
., 1990; reviewed by Armour, 1996)
and allele length analysis has demonstrated germline mutation rates as high as
15% per gamete (Jeffreys
et al
., 1988; Jeffreys, 1997). Minisatellite mutation may
involve intra-allelic rearrangements whose frequency, unlike inter-allelic
rearrangements, is influenced by the size of the tandem array (Buard
et al
., 1998).
Sequence similarities, manifested by a subset of minisatellites, to the Chi recom-
bination promoting element of
E. coli
have led to the suggestion that this 'core
sequence' might be recombinogenic and could serve to promote unequal crossing
over. However, analysis of flanking polymorphisms has not indicated the
exchange of markers predicted for the products of unequal exchange between alle-
les (Wolff
et al
., 1988, 1989). This notwithstanding, recombination hotspots some-
times co-localize with minisatellites (Jeffreys
et al
., 1998a) which has led to the
suggestion that minisatellite instability may be a by-product of meiotic recombi-
nation (Jeffreys
et al
., 1998b).
Monckton
et al
. (1994) have shown that minisatellite mutation can involve
complex inter-allelic gene conversion events. These may exhibit polarity since the
gain of a few repeat units appears to be confined to one end of the tandem repeat
array (Jeffreys
et al
., 1994). One alternative proposal is that minisatellite mutation
may involve an array homogenization process which could operate by biased
repair of intra-helical (slippage) or inter-helical (unequal sister chromatid
exchange) heteroduplexes (Bouzekri
et al
., 1998). Whatever the mechanism(s)
underlining their allelic variability, the rapid evolution of minisatellites appears
to have rendered them an important substrate for the opportunistic processes of
molecular evolution. Indeed, several are known to have become recruited as gene
regulatory elements (see Chapter 5, section 5.1.12,
Minisatellites and microsatellites
).
8.8.2 Microsatellite DNA sequences
Microsatellites typically mutate with a frequency of 10
-3
to 10
-4
although mutation
rates vary between loci by several orders of magnitude (Brinkman
et al
., 1998;
Crawford and Cuthbertson 1996). Microsatellite mutation events in the male
germline outnumber those in the female germline 5- to 6-fold (Brinkman
et al
.,
1998). Interestingly, alternative alleles at the same locus may differ dramatically
in terms of their mutation rate (Jin
et al
., 1996). By contrast, microsatellite loca-
tion is often conserved at orthologous positions in the genomes of different
species (Blanquer-Maumont and Crouau-Roy, 1995; Liao and Weiner, 1995;
Meyer
et al
., 1995; Moore
et al
., 1991; Pausova
et al
., 1995; Stallings
et al
., 1991;
Stallings, 1994, 1995; Sun and Kirkpatrick, 1996). Rubinsztein
et al
. (1995a,b)
compared allele length distributions for a considerable number of human
microsatellites with their orthologues in chimpanzees, gorillas, orangutans,
baboons, and macaques and claimed a tendency for the loci to be longer in
humans. Although some microsatellites are more variable in nonhuman primates
than in humans (Kayser
et al
., 1995), a tendency for the loci to be longer in humans
would be consistent with the directionality of microsatellite evolution and com-
patible with evolution proceeding at different rates in different species. However,
it could also be due to ascertainment bias in that it is precisely the longest, most
