Assignment of Atlantic salmon (Salmo salar) Linkage Groups to Specific Chromosomes: Conservation of Large Syntenic Blocks Corresponding to Whole Chromosome Arms in Rainbow Trout (Oncorhynchus mykiss)

Background: Most teleost species, especially freshwater groups such as the Esocidae which are theclosest relatives of salmonids, have a karyotype comprising 25 pairs of acrocentric chromosomes and 48–52 chromosome arms. After the common ancestor of salmonids underwent a whole genome duplication,its karyotype would have 100 chromosome arms, and this is reflected in the modal range of 96–104 seenin extant salmonids (e.g., rainbow trout). The Atlantic salmon is an exception among the salmonids as ithas 72–74 chromosome arms and its karyotype includes 12 pairs of large acrocentric chromosomes, whichappear to be the result of tandem fusions. The purpose of this study was to integrate the Atlantic salmon\u27slinkage map and karyotype and to compare the chromosome map with that of rainbow trout.Results: The Atlantic salmon genetic linkage groups were assigned to specific chromosomes in theEuropean subspecies using fluorescence in situ hybridization with BAC probes containing genetic markersmapped to each linkage group. The genetic linkage groups were larger for metacentric chromosomescompared to acrocentric chromosomes of similar size. Comparison of the Atlantic salmon chromosomemap with that of rainbow trout provides strong evidence for conservation of large syntenic blocks in thesespecies, corresponding to entire chromosome arms in the rainbow trout.Conclusion: It had been suggested that some of the large acrocentric chromosomes in Atlantic salmonare the result of tandem fusions, and that the small blocks of repetitive DNA in the middle of the armsrepresent the sites of chromosome fusions. The finding that the chromosomal regions on either side ofthe blocks of repetitive DNA within the larger acrocentric chromosomes correspond to different rainbowtrout chromosome arms provides support for this hypothesis

Assignment of Rainbow Trout Linkage Groups to Specific Chromosomes

The rainbow trout genetic linkage groups have been assigned to specific chromosomes in the OSU (2N = 60) strain using fluorescence in situ hybridization (FISH) with BAC probes containing genes mapped to each linkage group. There was a rough correlation between chromosome size and size of the genetic linkage map in centimorgans for the genetic maps based on recombination from the female parent. Chromosome size and structure have a major impact on the female:male recombination ratio, which is much higher (up to 10:1 near the centromeres) on the larger metacentric chromosomes compared to smaller acrocentric chromosomes. Eighty percent of the BAC clones containing duplicate genes mapped to a single chromosomal location, suggesting that diploidization resulted in substantial divergence of intergenic regions. The BAC clones that hybridized to both duplicate loci were usually located in the distal portion of the chromosome. Duplicate genes were almost always found at a similar location on the chromosome arm of two different chromosome pairs, suggesting that most of the chromosome rearrangements following tetraploidization were centric fusions and did not involve homeologous chromosomes. The set of BACs compiled for this research will be especially useful in construction of genome maps and identification of QTL for important traits in other salmonid fishes

A toolbox for the generation of chemical probes for Baculovirus IAP Repeat containing proteins

E3 ligases constitute a large and diverse family of proteins that play a central role in regulating protein homeostasis by recruiting substrate proteins via recruitment domains to the proteasomal degradation machinery. Small molecules can either inhibit, modulate or hijack E3 function. The latter class of small molecules led to the development of selective protein degraders, such as PROTACs (PROteolysis TArgeting Chimeras), that recruit protein targets to the ubiquitin system leading to a new class of pharmacologically active drugs and to new therapeutic options. Recent efforts have focused on the E3 family of Baculovirus IAP Repeat (BIR) domains that comprise a structurally conserved but diverse 70 amino acid long protein interaction domain. In the human proteome, 16 BIR domains have been identified, among them promising drug targets such as the Inhibitors of Apoptosis (IAP) family, that typically contain three BIR domains (BIR1, BIR2, and BIR3). To date, this target area lacks assay tools that would allow comprehensive evaluation of inhibitor selectivity. As a consequence, the selectivity of current BIR domain targeting inhibitors is unknown. To this end, we developed assays that allow determination of inhibitor selectivity in vitro as well as in cellulo. Using this toolbox, we have characterized available BIR domain inhibitors. The characterized chemical starting points and selectivity data will be the basis for the generation of new chemical probes for IAP proteins with well-characterized mode of action and provide the basis for future drug discovery efforts and the development of PROTACs and molecular glues

Heated gas bubbles enrich, crystallize, dry, phosphorylate and encapsulate prebiotic molecules

Non-equilibrium conditions must have been crucial for the assembly of the first informational polymers of early life, by supporting their formation and continuous enrichment in a long-lasting environment. Here, we explore how gas bubbles in water subjected to a thermal gradient, a likely scenario within crustal mafic rocks on the early Earth, drive a complex, continuous enrichment of prebiotic molecules. RNA precursors, monomers, active ribozymes, oligonucleotides and lipids are shown to (1) cycle between dry and wet states, enabling the central step of RNA phosphorylation, (2) accumulate at the gas-water interface to drastically increase ribozymatic activity, (3) condense into hydrogels, (4) form pure crystals and (5) encapsulate into protecting vesicle aggregates that subsequently undergo fission. These effects occur within less than 30 min. The findings unite, in one location, the physical conditions that were crucial for the chemical emergence of biopolymers. They suggest that heated microbubbles could have hosted the first cycles of molecular evolution