Holding it together: rapid evolution and positive selection in the synaptonemal complex of Drosophila

Background The synaptonemal complex (SC) is a highly conserved meiotic structure that functions to pair homologs and facilitate meiotic recombination in most eukaryotes. Five Drosophila SC proteins have been identified and localized within the complex: C(3)G, C(2)M, CONA, ORD, and the newly identified Corolla. The SC is required for meiotic recombination in Drosophila and absence of these proteins leads to reduced crossing over and chromosomal nondisjunction. Despite the conserved nature of the SC and the key role that these five proteins have in meiosis in D. melanogaster, they display little apparent sequence conservation outside the genus. To identify factors that explain this lack of apparent conservation, we performed a molecular evolutionary analysis of these genes across the Drosophila genus. Results For the five SC components, gene sequence similarity declines rapidly with increasing phylogenetic distance and only ORD and C(2)M are identifiable outside of the Drosophila genus. SC gene sequences have a higher dN/dS (ω) rate ratio than the genome wide average and this can in part be explained by the action of positive selection in almost every SC component. Across the genus, there is significant variation in ω for each protein. It further appears that ω estimates for the five SC components are in accordance with their physical position within the SC. Components interacting with chromatin evolve slowest and components comprising the central elements evolve the most rapidly. Finally, using population genetic approaches, we demonstrate that positive selection on SC components is ongoing. Conclusions SC components within Drosophila show little apparent sequence homology to those identified in other model organisms due to their rapid evolution. We propose that the Drosophila SC is evolving rapidly due to two combined effects. First, we propose that a high rate of evolution can be partly explained by low purifying selection on protein components whose function is to simply hold chromosomes together. We also propose that positive selection in the SC is driven by its sex-specificity combined with its role in facilitating both recombination and centromere clustering in the face of recurrent bouts of drive in female meiosis

Nimulid efficacy and tolerability in patients with rheumatic diseases

Objective. To study efficacy and safety of nimulid. Material and Methods. 33 pts with different rheumatic and vascular diseases were included in an open clinical trial of nimulid. Nimulid was administered 100-200 mg/day during 30 days. Disease modifying therapy was remained unchanged. Clinical and laboratory parameters were assessed before the start and after the end of therapy. Results. Significant improvement of all joint symptoms was achieved. 22(66,6%) pts showed good and 11(33,3%) - fair effect. Adverse events revealed in 5(7%) pts were mild and did not lead to the drug withdrawal. All adverse events were completely reversible. Conclusion. Our data show high efficacy and good tolerability of nimulid in this pts category