The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.

The inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management

Population and distribution of beavers Castor fiber

1. A century ago, overhunting had reduced Eurasian beaver Castor fiber populations to c. 1200 animals in scattered refugia from France to Mongolia. Reintroductions and natural spread have since restored the species to large areas of its original range. Population has more than tripled since the first modern estimate in 1998; the minimum estimate is now c. 1.5 million. 2. Range expansion 2000–2020 has been rapid, with large extensions in western and south-central Europe, southern Russia, and west and central Siberia. Beavers are now re-established in all countries of their former European range except for Portugal, Italy, and the southern Balkans; they occur broadly across Siberia to Mongolia, with scattered populations father east. About half of the world population lives in Russia. Populations appear to be mature in much of European Russia, Belarus, the Baltic States, and Poland. 3. There is a significant population of North American beaver Castor canadensis in Finland and north-west Russia. Most other 20th-Century introductions of this species have become extinct or been removed. 4. Recent DNA studies have improved understanding of Castor fiber population prehistory and history. Two clades, east and west, are extant; a third ‘Danube’ clade is extinct. Refugial populations were strongly bottlenecked, with loss of genetic diversity through genetic drift. 5. Future range extension, and large increases in populations and in impacts on freshwater systems, can be expected. Beavers are now recolonising densely populated, intensely modified, low-relief regions, such as England, the Netherlands, Belgium, and north-west Germany. They will become much more common and widespread there in coming decades. As beavers are ecosystem engineers with profound effects on riparian habitats, attention to integrating beaver management into these landscapes using experience gained in other areas – before the rapid increase in population densities and impacts occurs – is recommended. beaver, Castor fiber, Castor canadensis, distribution, Eurasia, population, reintroductionpublishedVersio

EU–Russia relations: between conflict and cooperation

EU–Russia relations have often been considered in scholarship to be governed by the dichotomy between conflict and cooperation. Cooperation has often coexisted or overlapped with conflict on a significant number of issues and policy areas, making relations between the two actors very complex. This article explores the dichotomy between conflict and cooperation, highlighting the way it has influenced the two actors’ policies towards the Eastern Neighbourhood. It posits that the difference between what the European Union (EU) says and what it does is desired and perpetuated both by Russia, the EU’s member states and the countries within the Eastern Neighbourhood. Simultaneously, Moscow is unable to formulate a clear strategy for the Eastern Neighbourhood, which makes its approach geared at providing short-term incentives to corrupt politicians in the countries in the region not sustainable in the long term. In doing so, the article also aims to enquire into the potential for EU–Russia relations to move beyond the well-known conflict–cooperation dichotomy