Molecular Genetics

Microscopic observations reveal an elaborate structure developing during pairing of homologous chromosomes in meiosis.

Facts

leptotene	early zygotene	late zygotene . . . pachytene	diplotene
Axial elements begin to decorate chromosomal fibers.	Axial elements approach one another, becoming lateral elements.	Mature synaptonemal complexes consist of a pair of paralell lateral elements flanking a central element. The elements are connected by transverse fibers.	Fewer nodules are present after desynapsis.

• Prophase of meiosis I occurs in morphologically distinguishable stages (above).
• The width of the synaptonemal complex (SC), 200 nm between axial elements, is 100 X the width of a DNA helix.
• Electron dense regions, called nodules, form at scattered sites along the SC.
  • In late pachytene there are twice as many nodules as in early diplotene, but they have different appearances, making it uncertain as to whether early nodules mature into late ones or late nodules arise de novo.
  • In diplotene, chromosomes appear physically linked at chiasmata.
  • The number of chiasmata is approximately the same as the number of late (diplotene) nodules.
  • The number of late nodules is approximately the same as the number of genetic cross-over events.
• Mutations in a gene called ZIP1 have interesting effects on the morphology of meiosis and genetic recombination
  • The width of the SC is increased by engineering the ZIP1 gene to produce a larger protein.
  • zip1 mutations only slightly interfere with chiasma formation and recombination.
  • zip1 mutations prevent mature SC formation and reduce cross-over interference (ref).
• Mutation in ZIP2 and ZIP3 genes prevents the initiation of the formation of synaptonemal complexes.
  • Their encoded proteins form a complex that binds to chromosomes.
  • Where they are bound is where synaptonemal complex formation inititates.
  • The distributions of ZIP2 foci on chromosomes suggests that these initiation complexes interfere with binding of additional foci in their vicinity (ref).

Interpretations

• Contrary to intuition, SC formation is not necessary for strand exchange between DNA duplexes.
• SC formation is necessary for cross over interference. However, the capacity for interference may also be determined early, during the formation of a syntaptonemal initiation complex.
• The ZIP1 protein binds lateral elements together. The central element may represent a region where ends of ZIP1 transverse fibers from opposite lateral elements overlap.
• Late nodules are precursors to chiasmata.
• Nodules may be the morphological sites of recombination (cross-over) events.
• Only half the events at nodules result in cross-overs. The other half may produce gene conversion events (without exchange of outside markers). The latter may occur earlier than recombination producing events (ref).

Further information

• Staining of meiotic maize nuclei with antibodies against RAD51, the eucaryotic homologue of recA revealed structures reminiscent of nodules. Many of these structures, but not all, disappeared before pachytene. The number of zygotene structures is much larger than the number of gene conversion events (ref). These observations also suggest that events leading to gene conversions are distinct from those leading to cross overs. Such a suggestion is inconsistent with molecular models of recombination.
• Synaptonemal complexes are not a feature of some organisms, such as Schizosaccharomyces pombe and Anacystis nidulans, that produce many chiasmata per chromosome.
• Current concepts of recombination are a synthesis of conclusions from morphological, genetic and molecular investigations.