Using a phylogenetic approach, the examination of 33 meiosis/meiosis-related genes in 12 Drosophila species, revealed nine independent gene duplications, involving the genes cav, mre11, meiS332, polo and mtrm. Evidence is provided that at least eight out of the nine gene duplicates are functional. Therefore, the rate at which Drosophila meiosis/meiosis-related genes are duplicated and retained is estimated to be 0.0012 per gene per million years, a value that is similar to the average for all Drosophila genes. It should be noted that by using a phylogenetic approach the confounding effect of concerted evolution, that is known to lead to overestimation of the duplication and retention rate, is avoided. This is an important issue, since even in our moderate size sample, evidence for long-term concerted evolution (lasting for more than 30 million years) was found for the meiS332 gene pair in species of the Drosophila subgenus. Most striking, in contrast to theoretical expectations, is the finding that genes that encode proteins that must follow a close stoichiometric balance, such as polo, mtrm and meiS332 have been found duplicated. The duplicated genes may be examples of gene neofunctionalization. It is speculated that meiosis duration may be a trait that is under selection in Drosophila and that it has different optimal values in different species.
Mms19 encodes a cytosolic iron-sulphur assembly component. We found that Drosophila Mms19 is also essential for mitotic divisions and for the proliferation of diploid cells. Reduced Mms19 activity causes severe mitotic defects in spindle dynamics and chromosome segregation, and loss of zygotic Mms19 prevents the formation of imaginal discs. The lack of mitotic tissue in Mms19P/P larvae can be rescued by overexpression of the Cdk-activating kinase (CAK) complex, an activator of mitotic Cdk1, suggesting that Mms19 functions in mitosis to allow CAK (Cdk7/Cyclin H/Mat1) to become fully active as a Cdk1-activating kinase. When bound to Xpd and TFIIH, the CAK subunit Cdk7 phosphorylates transcriptional targets and not cell cycle Cdks. In contrast, free CAK phosphorylates and activates Cdk1. Physical and genetic interaction studies between Mms19 and Xpd suggest that their interaction prevents Xpd from binding to the CAK complex. Xpd bound to Mms19 therefore frees CAK complexes, allowing them to phosphorylate Cdk1 and facilitating progression to metaphase. The structural basis for the competitive interaction with Xpd seems to be the binding of Mms19, core TFIIH and CAK to neighbouring or overlapping regions of Xpd.
We have previously characterized an EMS-induced allele of the bubR1 gene (bubR1D1326N) that separates the two functions of BubR1, causing meiotic nondisjunction but retaining spindle assembly checkpoint activity during somatic cell division in Drosophila melanogaster. Using this allele, we demonstrate that bubR1 meiotic nondisjunction is dosage sensitive, occurs for both exchange and nonexchange homologous chromosomes, and is associated with decreased maintenance of sister chromatid cohesion and of the synaptonemal complex during prophase I progression. We took advantage of these features to perform a genetic screen designed to identify third chromosome deficiencies having a dominant effect on bubR1D1326N/bubR1rev1 meiotic phenotypes. We tested 65 deficiencies covering 60% of the third chromosome euchromatin. Among them, we characterized 24 deficiencies having a dominant effect on bubR1D1326N/bubR1rev1 meiotic phenotypes that we classified in two groups: (1) suppressor of nondisjunction and (2) enhancer of nondisjunction. Among these 24 deficiencies, our results show that deficiencies uncovering the polo locus act as suppressor of bubR1 nondisjunction by delaying meiotic prophase I progression and restoring chiasmata formation as observed by the loading of the condensin subunit SMC2. Furthermore, we identified two deficiencies inducing a lethal phenotype during embryonic development and thus affecting BubR1 kinase activity in somatic cells and one deficiency causing female sterility. Overall, our genetic screening strategy proved to be highly sensitive for the identification of modifiers of BubR1 kinase activity in both meiosis and mitosis.
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