Growth, Differentiation and Sexuality

422 D. Zickler
– First, chiasma and RNs never occur uniformly
along chromosome arms, with a lesser
tendency to occur around centromeres and
a greater tendency to occur in the middle of
arms and/or in sub-telomeric regions (for
mycelial fungi, see Zickler 1977; Holm et al.
1981; Bojko 1989; Zickler et al. 1992; reviewed
in von Wettstein et al. 1984; Zickler and
Kleckner 1999). Also, short chromosomes
have higher number of COs per physical length
than do longer chromosomes (Mautino et al.
1993; Kaback et al. 1999). This non-random
distribution along chromosomes is already
reflected by the distribution of DSBs. They
occurathigherfrequenciesinsomegenomic
regions called hotspots, and at lower frequencies
in other regions called coldspots (review
in Petes 2001). Position of hotspots/DSBs may
be regulated by chromatin structure. They
are located in accessible (DNaseI-sensitive)
regions of the chromatin and in chromosome
domains that are GC-rich, whereas coldspots
are often associated with centromere, telomere
and AT-rich regions (Baudat and Nicolas
1997; Gerton et al. 2000). This is confirmed
by moving hotspot domains at various places
along a chromosome; formation of DSBs
is also controlled by distant cis and trans
interactions (e.g., Wu and Lichten 1995). Most
hotspots are intergenic, rather than intragenic.
Meiotic recombination can also be regionally
regulated, as in N. crassa and S. pombe (e.g., de
Veaux and Smith 1994; Yeadon et al. 2004).
– Second, each pair of homologous chromosomeswillhaveatleastoneCO/chiasma.This
“obligatory chiasma” occurs irrespective of
chromosome length, and is likely related to
the fact that at least one chiasma is necessary
to ensure regular segregation of the maternal
and paternal homologous chromosomes at division
I. The average number of chiasmata per
bivalent being rather small in most organisms
(see King and Mortimer 1990 for examples),
this obligatory event is achieved by tight
regulation. There are, however, two known
exceptions: S. pombe and A. nidulans. Inboth
organisms, the number of COs per meiosis
and per chromosome is high enough, so that
the probability that the smallest chromosome
gets no CO is extremely low (2 ×10 −5 for S.
pombe; review in Kohli and Bähler 1994).
– Third, when two genetic intervals are considered,
the presence of a CO at one position
is accompanied by a decreased probability
that another will occur nearby (for fungi,
see Strickland 1958; Perkins 1962; Perkins
et al. 1993; Munz 1994). Also, if two or more
chiasmataarepresentalongabivalent,they
exhibit interference and, therefore, a tendency
for even spacing. The strength of this interference
is inversely correlated with distance
(review in Jones 1984; Foss et al. 1993). By
contrast, NCOs do not show interference,
regardless of whether they are associated
with COs (Mortimer and Fogel 1974). Also,
chromatid interference (the fact that the
choice of a non-sister chromatid involved in
an exchange might influence the choice to be
involved in another close exchange) was found
to be absent or very rare (Perkins 1962; Esser
and Kuenen 1967; Mortimer and Fogel 1974).
The mechanism that regulates interference is not
understood, although several models have been
proposed.Thecountingmodel proposes thatafixed
number of NCOs separate COs (Foss et al. 1993).
Another model suggests that interference signals
initiate at sites of COs and spread outward along
the synaptonemal complex (SC; see Sect. V.), repressing
additional COs in the neighborhood, in
agreement with the fact that interference is not observed
between intervals that are far apart (King
and Mortimer 1990). The SC model has received
support from two findings: (1) the parallel absence
of CO interference and SC in A. nidulans and S.
pombe (Strickland 1958; Egel-Mitani et al. 1982;
Bähler et al. 1993; Munz 1994), and (2) the parallel
absence of SC and CO interference in the zip1
mutant of budding yeast, Zip1p being an essential
structural component of the SC central region
(Sym and Roeder 1994; Fung et al. 2004). However,
recent studies indicate that the SC is not required
for interference in budding yeast and Drosophila,
leaving the subject open for further explanations
(see Bishop and Zickler 2004).
IV. Homologue Recognition and Pairing
Juxtaposition of homologous chromosomes is
a prominent universal feature of meiosis. It
involves a long-distance recognition of homology,
which occurs no later than leptotene, in advance
of SC formation. Pairing, namely, the distinction
between “self” and “non-self”, is therefore
a fundamental biological problem. However, the