Gene duplication is an important source of evolutionary novelty Most duplications are of just a single gene, but Ohno proposed that whole-genome duplication (polyploidy) is an important evolutionary mechanism Many duplicate genes have been found in Saccharomyces cerevisiae, and these often seem to be phenotypically redundant Here we show that the arrangement of duplicated genes in the S cerevisiae genome is consistent with Ohno's hypothesis We propose a model in which this species is a degenerate tetraploid resulting from a whole-genome duplication that occurred after the divergence of Saccharomyces from Kluyveromyces Only a small fraction of the genes were subsequently retained in duplicate (most were deleted), and gene order was rearranged by many reciprocal translocations between chromosomes Protein pairs derived from this duplication event make up 13% of all yeast proteins, and include pairs of transcription factors, protein kinases, myosins, cyclins and pheromones Tetraploidy may have facilitated the evolution of anaerobic fermentation in Saccharomyces

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Molecular evidence for an ancient duplication of the entire yeast genome

Polymeric micelles are demonstrating high potential as nanomedicines capable of controlling the distribution and function of loaded bioactive agents in the body, effectively overcoming biological barriers, and various formulations are engaged in intensive preclinical and clinical testing. This Review focuses on polymeric micelles assembled through multimolecular interactions between block copolymers and the loaded drugs, proteins, or nucleic acids as translationable nanomedicines. The aspects involved in the design of successful micellar carriers are described in detail on the basis of the type of polymer/payload interaction, as well as the interplay of micelles with the biological interface, emphasizing on the chemistry and engineering of the block copolymers. By shaping these features, polymeric micelles have been propitious for delivering a wide range of therapeutics through effective sensing of targets in the body and adjustment of their properties in response to particular stimuli, modulating the act...

Block Copolymer Micelles in Nanomedicine Applications.

▪ Abstract Telomeres are DNA and protein structures that form complexes protecting the ends of chromosomes. Understanding of the mechanisms maintaining telomeres and insights into their function have advanced considerably in recent years. This review summarizes the currently known components of the telomere/telomerase functional complex, and focuses on how they act in the control of processes occurring at telomeres. These include processes acting on the telomeric DNA and on telomeric proteins. Key among them are DNA replication and elongation of one telomeric DNA strand by telomerase. In some situations, homologous recombination of telomeric and subtelomeric DNA is induced. All these processes act to replenish or restore telomeres. Conversely, degradative processes that shorten telomeric DNA, and nonhomologous end-joining of telomeric DNA, can lead to loss of telomere function and genomic instability. Hence they too must normally be tightly controlled.

Telomeres and their control

RNA-based therapeutics, such as small-interfering (siRNAs), microRNAs (miRNAs), antisense oligonucleotides (ASOs), aptamers, synthetic mRNAs and CRISPR-Cas9, have great potential to target a large part of the currently undruggable genes and gene products and to generate entirely new therapeutic paradigms in disease, ranging from cancer to pandemic influenza to Alzheimer's disease. However, for these RNA modalities to reach their full potential, they first need to overcome a billion years of evolutionary defenses that have kept RNAs on the outside of cells from invading the inside of cells. Overcoming the lipid bilayer to deliver RNA into cells has remained the major problem to solve for widespread development of RNA therapeutics, but recent chemistry advances have begun to penetrate this evolutionary armor.

Overcoming cellular barriers for RNA therapeutics

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

FDA-Approved Oligonucleotide Therapies in 2017

Regulation of monocyte chemoattractant protein-1 by the oxidized lipid, 13-hydroperoxyoctadecadienoic acid, in vascular smooth muscle cells via nuclear factor–kappa B (NF-кB)

Antisense oligonucleotides (ASOs) are known to trigger mRNA degradation in the nucleus via an RNase H-dependent mechanism. We have now identified a putative cytoplasmic mechanism through which ASO gapmers silence their targets when transfected or delivered gymnotically (i.e. in the absence of any transfection reagent). We have shown that the ASO gapmers can interact with the Ago-2 PAZ domain and can localize into GW-182 mRNA-degradation bodies (GW-bodies). The degradation products of the targeted mRNA, however, are not generated by Ago-2-directed cleavage. The apparent identification of a cytoplasmic pathway complements the previously known nuclear activity of ASOs and concurrently suggests that nuclear localization is not an absolute requirement for gene silencing.

Daniela Castanotto

Papers

FDA-Approved Oligonucleotide Therapies in 2017

Regulation of monocyte chemoattractant protein-1 by the oxidized lipid, 13-hydroperoxyoctadecadienoic acid, in vascular smooth muscle cells via nuclear factor–kappa B (NF-кB)

A cytoplasmic pathway for gapmer antisense oligonucleotide-mediated gene silencing in mammalian cells

Amplification of RNAi--targeting HLA mRNAs.

Oligonucleotides to the (Gene) Rescue: FDA Approvals 2017–2019