Dispersive forces and resisting spot welds by alternative homolog conjunction govern chromosome shape in Drosophila spermatocytes during prophase I

Abstract

The bivalent chromosomes that are generated during prophase of meiosis I comprise a pair of homologous chromosomes. Homolog pairing during prophase I must include mechanisms that avoid or eliminate entanglements between non-homologous chromosomes. In Drosophila spermatocytes, non-homologous associations are disrupted by chromosome territory formation, while linkages between homologous chromosomes are maintained by special conjunction proteins. These proteins function as alternative for crossovers that link homologs during canonical meiosis but are absent during the achiasmate Drosophila male meiosis. How and where within bivalents the alternative homolog conjunction proteins function is still poorly understood. To clarify the rules that govern territory formation and alternative homolog conjunction, we have analyzed spermatocytes with chromosomal aberrations. We examined territory formation after acute chromosome cleavage by Cas9, targeted to the dodeca satellite adjacent to the centromere of chromosome 3 specifically in spermatocytes. Moreover, we studied territory organization, as well as the eventual orientation of chromosomes during meiosis I, in spermatocytes with stable structural aberrations, including heterozygous reciprocal autosomal translocations. Our observations indicate that alternative homolog conjunction is applied in a spatially confined manner. Comparable to crossovers, only a single conjunction spot per chromosome arm appears to be applied usually. These conjunction spots resist separation by the dispersing forces that drive apart homologous pericentromeric heterochromatin and embedded centromeres within territories, as well as the distinct chromosomal entities into peripheral, maximally separated territories within the spermatocyte nucleus.

Teflon promotes chromosomal recruitment of homolog conjunction proteins during Drosophila male meiosis

“…Do these dots mark the location of autosomal homolog conjunction, or might there be additional SUM complexes at other locations below the limit of detection that contribute to conjunction as well? Recent cytological analyses of meiotic quadrivalents in spermatocytes heterozygous for autosomal translocations have indicated that autosomal homolog conjunction is spatially constrained to dot-like chromosomal locations [ 36 ]. The spatial control of autosomal homolog conjunction in spermatocytes appears to be analogous to that of canonical crossovers.…”

“…The spatial control of autosomal homolog conjunction in spermatocytes appears to be analogous to that of canonical crossovers. As a rule, a single restricted region within the euchromatic portion of each autosomal chromosome arm is linked by AHC protein assemblies to its homologous region [ 36 ]. Thus, AHC positions might be controlled by processes analogous to crossover interference.…”

Homologous chromosomes are stably conjoined for Drosophila male meiosis I by SUM, a multimerized protein assembly with modules for DNA-binding and for separase-mediated dissociation co-opted from cohesin

“…During chromosome condensation at the onset of the first meiotic division (M I), the sub-nucleolar SUM foci coalesce into a single large dot at the XY chromosome (chr) pairing site [ 20 , 22 ]. On autosomal bivalents, the SUM proteins are present in much smaller dots that are not necessarily always detectable above background [ 20 , 22 , 23 , 27 ]. The number of SUM dots on autosomal bivalents appears to be restricted to around one or two per bivalent at the start of M I [ 23 , 27 ].…”

“…On autosomal bivalents, the SUM proteins are present in much smaller dots that are not necessarily always detectable above background [ 20 , 22 , 23 , 27 ]. The number of SUM dots on autosomal bivalents appears to be restricted to around one or two per bivalent at the start of M I [ 23 , 27 ]. Their chromosomal localization is presumably distinct in each spermatocyte, as genetic analyses have revealed a wide-spread distribution of meiotic conjunction potential throughout the euchromatic regions rather than dedicated invariant autosomal conjunction sites [ 28 , 29 ].…”

“…Their chromosomal localization is presumably distinct in each spermatocyte, as genetic analyses have revealed a wide-spread distribution of meiotic conjunction potential throughout the euchromatic regions rather than dedicated invariant autosomal conjunction sites [ 28 , 29 ]. Possibly, therefore, AHC is established during spermatocyte maturation in a rather randomly chosen restricted chromosomal region in case of autosomal bivalents, analogous to the placement of COs during canonical meiosis [ 27 ]. Strong support for the notion that the SUM protein dots on the sex chromosome and autosomal bivalents represent the physical conjunction between chromosomes is their precipitous, separase-dependent disappearance at the onset of anaphase I [ 20 , 22 , 30 ].…”