Growth, Differentiation and Sexuality

432 D. Zickler
mechanism by which chiasmata are formed and
maintained through chromosome condensation.
Another important aspect of meiosis to be solved
is cell progression. Several studies indicate that
the cell cycle machinery that controls progression
through mitosis is also used to regulate progression
through meiosis (review in Lee and Amon 2001).
However, most meiosis-specific modifications of
the mitotic cycle remain largely uncharacterized.
Also, very little is known concerning the metabolic
requirements ensuring correct meiotic and/or
sporulation progression. For example, why do P.
anserina mutants defective for the mitochondrial
citrate synthase arrest at the diffuse stage, a major
landmark of oogenesis (Ruprich-Robert et al.
2002)? In short, the discovery of new proteins
involved in the meiotic process often simultaneously
provides satisfying answers to long-standing
questions in chromosome biology, while revealing
a new set of puzzles to solve.
The most important research progress has
been made in budding yeast because genetic,
physiology, cytology and biochemistry were used
in combination. Although meiosis is a highly
conserved process, recent comparative studies
(e.g., with S. pombe, C. cinereus, S. macrospora,
among the fungi) have provided informative
variations in the mechanisms used by different
organisms. Also, recent findings in N. crassa
support the notion that an important barrier
between two closely related species is, in fact, the
existence of numerous small rearrangements in
the genome (Shiu et al. 2001). Future studies will
likely make use of genome-sequencing projects to
identify homologues to important proteins from
other species (e.g., Borkovich et al. 2004). With
the availability of yeast homologues to fungal,
plant and animal genes, it will be possible to
use immunolocalization and newly established
reverse genetic strategies to determine whether
there are functional similarities across organisms.
Although promising, it is also clear that several
structural proteins with analogous functions do
not share apparent sequence similarities (e.g., SC
components and proteins that initiate recombination
or protect centromeric cohesins, see above).
A complete understanding of the mechanisms
of chromosome recognition and segregation will
continue to require synergistic approaches, integrating
structural information with biochemical
experimentation. In addition, it will be important
to pursue forward genetic approaches in combination
with high-resolution cytological analyses to
identify genes that have conserved roles but also
genes that have roles unique to fungal meiosis.
After we have defined more precisely the function
of several genes, we will have to solve the mystery
of how the meiotic process evolved. Whether we
will ever be able to answer this question may
depend on the finding of missing links that may
exist in the vast fungal kingdom.
Acknowledgements.This review is dedicated to the memory
of Georges Rizet. He introduced P. anserina and A. immersus
as model organisms. Both provided fundamental information
concerning meiotic recombination, vegetative incompatibility,
cytoplasmic inheritance and senescence that
would have been difficult to obtain from other species commonly
used as model systems. He was a superb investigator
whose genetic experiments were exemplary in design and
execution, and I was fortunate to do my thesis in his laboratory.
I am also deeply grateful to David Perkins for his steady
interest in my work. I apologize to 1 the colleagues whose
work was not cited or discussed, due to limits imposed by
the book format.
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