Opsin proteins are fundamental components of animal vision whose structure largely determines the sensitivity of visual pigments to different wavelengths of light. Surprisingly little is known about opsin evolution in beetles, even though they are the most species rich animal group on Earth and exhibit considerable variation in visual system sensitivities. We reveal the patterns of opsin evolution across 62 beetle species and relatives. Our results show that the major insect opsin class (SW) that typically confers sensitivity to "blue" wavelengths was lost ~300 million years ago, before the origin of modern beetles. We propose that UV and LW opsin gene duplications have restored the potential for trichromacy (three separate channels for colour vision) in beetles up to 12 times and more specifically, duplications within the UV opsin class have likely led to the restoration of "blue" sensitivity up to 10 times. This finding reveals unexpected plasticity within the insect visual system and highlights its remarkable ability to evolve and adapt to the available light and visual cues present in the environment.At the molecular level, the wavelength sensitivity of an animal photoreceptor is determined by the photopigment, comprising an opsin protein bound to a light-absorbing chromophore. Insects commonly possess three opsin proteins (UV, SW and LW) that form photopigments maximally sensitive to ultraviolet (~350 nm), blue (~440 nm) and green (~530 nm) wavelengths, respectively. As insect opsin genes form distinct phylogenetic clades according to their spectral class (UV, SW or LW) the sensitivity ranges of an insect visual system can usually be estimated by the complement of opsin genes present. In some insects photopigment sensitivity has extended outside of this range into the violet (~420 nm) and red (>600 nm) region of the light spectrum through duplications of the SW 1,2 and LW opsins 2,3

Activating transcription factor (ATF) 5 is a transcription factor belonging to the ATF/cAMP-response element-binding protein gene family. We previously reported that ATF5 mRNA expression increased in response to amino acid limitation. The ATF5 gene allows transcription of mRNAs with at least two alternative 5-untranslated regions (5-UTRs), 5-UTR␣ and 5-UTR␤, derived from exon1␣ and exon1␤. 5-UTR␣ contains highly conserved sequences, in which the upstream open reading frames (uORFs) uORF1 and uORF2 are found in many species. This study was designed to investigate the potential role of 5-UTRs in translational control. These 5-UTRs differentially determined translation efficiency from mRNA. The presence of 5-UTR␣ or 5-UTR␤ represses translation from the downstream ATF5 ORF. Moreover, 5-UTR␣-regulated translational repression is released by amino acid limitation or NaAsO 2 exposure. This release was not seen for 5-UTR␤. Mutation of uAUG2 in the uORF2 of 5-UTR␣ restored the basal expression and abolished the positive regulation by amino acid limitation or arsenite exposure. We demonstrated that phosphorylation of eukaryotic initiation factor 2␣ was required for amino acid limitation-induced translational regulation of ATF5. Furthermore, arsenite exposure activated the exogenously expressed hemeregulated inhibitor kinase and induced the phosphorylation of eukaryotic initiation factor 2␣ in nonerythroid cells. These results suggest that translation of ATF5 is regulated by the alternative 5-UTR region of its mRNA, and ATF5 may play a role in protecting cells from amino acid limitation or arsenite-induced oxidative stress.Activating transcription factor (ATF) 2 -5 (formerly designated ATFx) is a transcription factor of the cAMP-response element-binding protein (CREB)/ATF family that was first identified as a protein that binds to the lipopolysaccharide-response element (GPE-1) on the granulocyte colony-stimulating factor (CSF3) gene along with C/EBP␥ (1). It contains a DNAbinding and dimerization domain (bZIP domain) and regulates processes that are involved in cellular differentiation (2, 3), the cell cycle (4), and apoptosis (5, 6). ATF5 represses cAMP-induced transcription in cultured cells (4) and is shown to inhibit apoptosis (6). Angelastro et al. (2) demonstrated that ATF5 inhibits CRE-mediated expression of neural genes and neural differentiation. Cdc34 is the G 2 checkpoint gene, and ATF5 is a target of Cdc34-dependent ubiquitin-mediated proteolysis (4), expression of which is affected by the cell cycle. Recently, Monaco et al. (7) showed that ATF5 is widely expressed in carcinomas, and interference with its function caused apoptotic cell death of neoplastic breast cell lines. This suggests that ATF5 may be a target for cancer therapy and that studies of the mechanism by which ATF5 expression is regulated might be important in the investigation of treatments for cancer.Mammalian cells have the ability to alter their gene expression to adapt to a variety of environmental stresses, including nutrient limitation, ...

Cell-penetrating peptides (CPPs) including arginine-rich peptides are attracting a lot of attention due to their potential as a novel intracellular drug delivery tool without substantial toxicity. On the other hand, disease-associated arginine-rich CPPs, such as poly-PR and poly-GR translated from C9orf72 gene, also efficiently enter neuronal cells and then kill them. Although both non-harmful CPPs and harmful poly-PR/GR penetrate the plasma membrane using same arginine residues, little is known about the factors which determine the toxicity of the pathogenic CPPs. Here, we show that poly-PR and poly-GR, but not other Arg-rich CPPs, specifically distributed to nucleolus via interaction with RNA. Importantly, C9orf72-dipeptides, but not other Arg-rich CPPs, caused inhibition of protein translation and cell death. Raising extracellular pH enhanced the cell penetration of poly-PR. The repeat number of (PR) affected the secondary structure and determined the intracellular delivery rate and neurotoxicity, and enforced intracellular delivery of non-penetrating short poly-PR peptide caused cell death, suggesting that modulation of extracellular environment to inhibit the uptake of Arg-rich dipeptides might be a drug target against poly-PR/GR-mediated neurotoxicity.

Gene duplication plays a central role in adaptation to novel environments by providing new genetic material for functional divergence and evolution of biological complexity. Several evolutionary models have been proposed for gene duplication to explain how new gene copies are preserved by natural selection, but these models have rarely been tested using empirical data. Opsin proteins, when combined with a chromophore, form a photopigment that is responsible for the absorption of light, the first step in the phototransduction cascade. Adaptive gene duplications have occurred many times within the animal opsins' gene family, leading to novel wavelength sensitivities. Consequently, opsins are an attractive choice for the study of gene duplication evolutionary models. Odonata (dragonflies and damselflies) have the largest opsin repertoire of any insect currently known. Additionally, there is tremendous variation in opsin copy number between species, particularly in the long-wavelength-sensitive (LWS) class. Using comprehensive phylotranscriptomic and statistical approaches, we tested various evolutionary models of gene duplication. Our results suggest that both the blue-sensitive (BS) and LWS opsin classes were subjected to strong positive selection that greatly weakens after multiple duplication events, a pattern that is consistent with the permanent heterozygote model. Due to the immense interspecific variation and duplicability potential of opsin genes among odonates, they represent a unique model system to test hypotheses regarding opsin gene duplication and diversification at the molecular level.

Introgression is an important biological process affecting at least 10% of the extant species in the animal kingdom. Introgression significantly impacts inference of phylogenetic species relationships where a strictly binary tree model cannot adequately explain reticulate net-like species relationships. Here we use phylogenomic approaches to understand patterns of introgression along the evolutionary history of a unique, non-model insect system: dragonflies and damselflies (Odonata). We demonstrate that introgression is a pervasive evolutionary force across various taxonomic levels within Odonata. In particular, we show that the morphologically “intermediate” species of Anisozygoptera (one of the three primary suborders within Odonata besides Zygoptera and Anisoptera), which retain phenotypic characteristics of the other two suborders, experienced high levels of introgression likely coming from zygopteran genomes. Additionally, we find evidence for multiple cases of deep inter-superfamilial ancestral introgression.