The evolution of immune-related genes from disease carrying mosquitoes: diversity in a peptidoglycan- and a thioester-recognizing protein.

Adaptive polymorphism may be common in immune system genes as co-evolutionary interactions foster diversity; either through ongoing positive selection (arms races), or balancing selection. DNA sequence diversity in two putative immune system genes was examined in species of the genus Anopheles and from Aedes aegypti. For one gene, encoding the peptidoglycan recognizing protein PGRPLB, there was evidence of purifying selection, suggesting that selection acts to eliminate sequence variation. For another gene, encoding the thioester-containing protein TEP3, higher levels of amino acid replacement were found than would be expected under neutral models of evolution - an indication that this gene has been subject to repeated bouts of positive selection.

A role for Drosophila SMC4 in the resolution of sister chromatids in mitosis.

BACKGROUND: Faithful segregation of the genome during mitosis requires interphase chromatin to be condensed into well-defined chromosomes. Chromosome condensation involves a multiprotein complex known as condensin that associates with chromatin early in prophase. Until now, genetic analysis of SMC subunits of the condensin complex in higher eukaryotic cells has not been performed, and consequently the detailed contribution of different subunits to the formation of mitotic chromosome morphology is poorly understood. RESULTS: We show that the SMC4 subunit of condensin is encoded by the essential gluon locus in Drosophila. DmSMC4 contains all the conserved domains present in other members of the structural-maintenance-of-chromosomes protein family. DmSMC4 is both nuclear and cytoplasmic during interphase, concentrates on chromatin during prophase, and localizes to the axial chromosome core at metaphase and anaphase. During decondensation in telophase, most of the DmSMC4 leaves the chromosomes. An examination of gluon mutations indicates that SMC4 is required for chromosome condensation and segregation during different developmental stages. A detailed analysis of mitotic chromosome structure in mutant cells indicates that although the longitudinal axis can be shortened normally, sister chromatid resolution is strikingly disrupted. This phenotype then leads to severe chromosome segregation defects, chromosome breakage, and apoptosis. CONCLUSIONS: Our results demonstrate that SMC4 is critically important for the resolution of sister chromatids during mitosis prior to anaphase onset.

The Drosophila RAD21 cohesin persists at the centromere region in mitosis.

'Cohesin' is a highly conserved multiprotein complex thought to be the primary effector of sister-chromatid cohesion in all eukaryotes. Cohesin complexes in budding yeast hold sister chromatids together from S phase until anaphase, but in metazoans, cohesin proteins dissociate from chromosomes and redistribute into the whole cell volume during prophase, well before sister chromatids separate (reviewed in [1,2]). Here we address this apparent anomaly by investigating the cell-cycle dynamics of DRAD21, the Drosophila orthologue of the Xenopus XRAD21 and Saccharomyces cerevisiae Scc1p/Mcd1p cohesins [3]. Analysis of DRAD21 in S2 Drosophila tissue culture cells and live embryos expressing a DRAD21-green fluorescent protein (GFP) fusion revealed the presence of four distinct subcellular pools of DRAD21: a cytoplasmic pool; a chromosome-associated pool which dissociates from chromatin as chromosomes condense in prophase; a short-lived centrosome-associated pool present during metaphase-anaphase; and a centromere-proximal pool which remains bound to condensed chromosomes, is found along the junction of sister chromatids between kinetochores, and persists until the metaphase-anaphase transition. We conclude that in Drosophila, and possibly all metazoans, a minor pool of cohesin remains bound to centromere-proximal chromatin after prophase and maintains sister-chromatid cohesion until the metaphase-anaphase transition.

Review: SMCs in the world of chromosome biology- from prokaryotes to higher eukaryotes.

The study of higher order chromosome structure and how it is modified through the course of the cell cycle has fascinated geneticists, biochemists, and cell biologists for decades. The results from many diverse technical avenues have converged in the discovery of a large superfamily of chromosome-associated proteins known as SMCs, for structural maintenance of chromosomes, which are predicted to have ATPase activity. Now found in all eukaryotes examined, and numerous prokaryotes as well, SMCs play crucial roles in chromatid cohesion, chromosome condensation, sex chromosome dosage compensation, and DNA recombination repair. In eukaryotes, SMCs exist in five subfamilies, which appear to associate with one another in particular pairs to perform their specific functions. In this review, we summarize current progress examining the roles these proteins, and the complexes they form, play in chromosome metabolism. We also present a twist in the SMC story, with the possibility of one SMC moonlighting in an unpredicted location.