Cells in multicellular organisms are genetically heterogeneous owing to somatic mutations. The accumulation of somatic genetic variation in species undergoing asexual (or clonal) reproduction (termed modular species) may lead to phenotypic heterogeneity among modules. However, abundance and dynamics of somatic genetic variation under clonal growth, a widespread life history in nature, remain poorly understood. Here we show that branching events in a seagrass clone or genet leads to population bottlenecks at the cellular level and hence the evolution of genetically differentiated modules. Studying inter-module somatic genetic variation, we uncovered thousands of SNPs that segregated among modules. The strength of purifying selection on mosaic genetic variation was greater at the intra-module comparing with the inter-module level. Our study provides evidence for the operation of selection at multiple levels, of cell population and modules. Somatic genetic drift leads to the emergence of genetically unique modules; hence, modules in long-lived clonal species constitute an appropriate elementary level of selection and individuality.All multicellular species, from plants to humans, are genetic mosaics, owing to mitotic errors (somatic mutations) during growth and development 1,2 . In unitary species, the resulting intra-organismal genetic heterogeneity may lead to genomic conflict and is often associated with degenerative disease such as cancer 3 (but see ref 4 ). Somatic genetic variation may play a different, more positive role in species undergoing asexual (or clonal) reproduction, hereafter called modular species, featured by 65% of all plant families 5 and 35% of all animal phyla 6 . Modular species have a simple body plan, and often indeterminate growth, during which iterative units (modules) emerge by asexual proliferation through fission, budding or branching 7 . Modules originating from the same zygote collectively form the clone or genet 8 . Under modular organization, somatic genetic variation may segregate when new modules are
Flushing toilet with seawater is an effective method for preserving freshwater resources, but it introduces iodide and bromide ions into domestic wastewater. During chlorine disinfection, iodide and bromide ions in the saline wastewater effluent lead to the formation of iodinated and brominated aromatic disinfection byproducts (DBPs). Examples of aromatic DBPs include iodophenolic, bromophenolic and chlorophenolic compounds, which generally display substantially higher toxicity than haloaliphatic DBPs. This paper presented for the first time the rates of phototransformation of 21 newly identified halophenolic DBPs in seawater, the receiving waterbody of the wastewater effluent. The phototransformation rate constants (k) were in the range from 7.75 × 10 −4 to 4.62 × 10 −1 h −1 , which gave half-lives of 1.5-895 h. A quantitative structureactivity relationship was established for the phototransformation of halophenolic DBPs as logk = − 0.0100 × ΔG f 0 + 5.7528 × logMW + 0.3686 × pKa − 19.1607,, whereΔG f 0 is standard Gibbs formation energy, MW is molecular weight, and pK a is dissociation constant. This model well predicted the k values of halophenolic DBPs. Among the tested DBPs, 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol were found to exhibit relatively high risks on marine organisms, based on toxicity indices and half-lives. In seawater, the two DBPs underwent photonucleophilic substitutions by bromide, chloride and hydroxide ions, resulting in the conversion to their bromophenolic and chlorophenolic counterparts (which are less toxic than the parent iodophenolic DBPs) and to their hydroxyphenolic counterparts (iodo(hydro)quinones, which are more toxic than the parent iodophenolic DBPs). The formed iodo(hydro)quinones further transformed to hydroxyliodo(hydro)quinones, which have lower toxicity than the parent compounds.
SARS-CoV-2 is the pathogen that caused the global COVID-19 outbreak in 2020. Promising progress has been made in developing vaccines and antiviral drugs. Antivirals medicines are necessary complements of vaccines for post-infection treatment. The main protease (Mpro) is an extremely important protease in the reproduction process of coronaviruses which cleaves pp1ab over more than 11 cleavage sites. In this work, two active main protease inhibitors were found via docking-based virtual screening and bioassay. The IC
50
of compound VS10 was 0.20 μM, and the IC
50
of compound VS12 was 1.89 μM. The finding in this work can be helpful to understand the interactions of main protease and inhibitors. The active candidates could be potential lead compounds for future drug design.
Mechanisms underlying the depletion of NAD+ and accumulation of reactive oxygen species (ROS) in aging and age‐related disorders remain poorly defined. We show that reverse electron transfer (RET) at mitochondrial complex I, which causes increased ROS production and NAD+ to NADH conversion and thus lowered NAD+/NADH ratio, is active during aging. Genetic or pharmacological inhibition of RET decreases ROS production and increases NAD+/NADH ratio, extending the lifespan of normal flies. The lifespan‐extending effect of RET inhibition is dependent on NAD+‐dependent Sirtuin, highlighting the importance of NAD+/NADH rebalance, and on longevity‐associated Foxo and autophagy pathways. RET and RET‐induced ROS and NAD+/NADH ratio changes are prominent in human induced pluripotent stem cell (iPSC) model and fly models of Alzheimer's disease (AD). Genetic or pharmacological inhibition of RET prevents the accumulation of faulty translation products resulting from inadequate ribosome‐mediated quality control, rescues relevant disease phenotypes, and extends the lifespan of Drosophila and mouse AD models. Deregulated RET is therefore a conserved feature of aging, and inhibition of RET may open new therapeutic opportunities in the context of aging and age‐related diseases including AD.
Currents are unique drivers of oceanic phylogeography and so determine the distribution of marine coastal species, along with past glaciations and sea level changes. Here, we reconstruct the worldwide colonization history of eelgrass (Zostera marina L.), the most widely distributed marine flowering plant or seagrass from its origin in the Northwest Pacific, based on nuclear and chloroplast genomes. We identified two divergent Pacific clades with evidence for admixture along the East Pacific coast. Multiple west to east (trans-Pacific) colonization events support the key role of the North Pacific Current. Time-calibrated nuclear and chloroplast phylogenies yielded concordant estimates of the arrival of Z. marina in the Atlantic through the Canadian Arctic, suggesting that eelgrass-based ecosystems, hotspots of biodiversity and carbon sequestration, have only been present since ~208 Kya (thousand years ago). Mediterranean populations were founded ~53 Kya while extant distributions along western and eastern Atlantic shores coincide with the end of the Last Glacial Maximum (~20 Kya). The recent colonization and 5- to 7-fold lower genomic diversity of Atlantic compared to the Pacific populations raises concern and opportunity about how Atlantic eelgrass might respond to rapidly warming coastal oceans.
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