Multicellular Eukaryotes Research Articles

The Negative Entropy in Organisms; Its Maintenance and Extension

Life has been a mystery for most physicists since the question of Maxwell’s demon. In the present paper, the self-reproduction, which is characteristic of the organism, is shown to be essential in resolving the paradox of Maxwell’s demon. For this purpose, a new thermodynamic quantity of biological activity is introduced to represent the molecular events in an organism recently revealed by molecular biology. This quantity gives a measure that the entropy production arising from the difference between acquired energy and stored energy compensates for the negative entropy of systematizing the organism, and is considered to be proportional to the self-reproducing rate of the organism as the first approximation. The equation of replicator dynamics consisting of self-reproducing rate, death rate and mutation terms contains all known types of evolution of unicellular organisms. When the mutation term is restricted to the point mutation mainly due to the nucleotide base changes in genes, this equation automatically leads to Darwinian evolution that the mutant with the higher increase rate is selected to become prevailing in the population. Throughout this evolution, the nucleotide bases in genes are converged to the special arrangement exhibiting the optimal increase rate of the organism. Moreover, the mutants having experienced gene duplication first decline to the minor members in the population but some of the descendants recover as a new style of organisms by generating new gene(s) from the counterpart of duplicated genes. This evolutionary process to expand the repertoire of genes is mathematically formulated by solving the equation of replicator dynamics up to the higher order of mutation terms. The present theoretical approach can be not only extended to the multicellular diploid eukaryotes but also applied to explain the origin of genes in the self-reproducing proto-cells formed anciently.

Isolation, taxonomic analysis, and phenotypic characterization of bacterial endophytes present in alfalfa (Medicago sativa) seeds

A growing body of evidence has reinforced the central role of microbiomes in the life of sound multicellular eukaryotes, thus more properly described as true holobionts. Though soil was considered a main source of plant microbiomes, seeds have been shown to be endophytically colonized by microorganisms thus representing natural carriers of a selected microbial inoculum to the young seedlings. In this work we have investigated the type of culturable endophytic bacteria that are carried within surface-sterilized alfalfa seeds. MALDI-TOF analysis revealed the presence of bacteria that belonged to 40 separate genera, distributed within four taxa (Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes). Nonsymbiotic members of the Rhizobiaceae family were also found. The evaluation of nine different in-vitro biochemical activities demonstrated isolates with complex combinations of traits that, upon a Principal-Component-Analysis, could be classified into four phenotypic groups. That isolates from nearly half of the genera identified had been able to colonize alfalfa plants grown under axenic conditions was remarkable. Further analyses should be addressed to investigating the colonization mechanisms of the alfalfa seeds, the evolutionary significance of the alfalfa-seed endophytes, and also how after germination the seed microbiome competes with spermospheric and rhizospheric soil bacteria to colonize newly emerging seedlings.

New Insights Into Beclin-1: Evolution and Pan-Malignancy Inhibitor Activity.

Autophagy is a functionally conserved self-degradation process that facilitates the survival of eukaryotic life via the management of cellular bioenergetics and maintenance of the fidelity of genomic DNA. The first known autophagy inducer was Beclin-1. Beclin-1 is expressed in multicellular eukaryotes ranging throughout plants to animals, comprising a nonmonophyllic group, as shown in this report via aggressive BLAST searches. In humans, Beclin-1 is a haploinsuffient tumor suppressor as biallelic deletions have not been observed in patient tumors clinically. Therefore, Beclin-1 fails the Knudson hypothesis, implicating expression of at least one Beclin-1 allele is essential for cancer cell survival. However, Beclin-1 is frequently monoallelically deleted in advanced human cancers and the expression of two Beclin-1 allelles is associated with greater anticancer effects. Overall, experimental evidence suggests that Beclin-1 inhibits tumor formation, angiogenesis, and metastasis alone and in cooperation with the tumor suppressive molecules UVRAG, Bif-1, Ambra1, and MDA-7/IL-24 via diverse mechanisms of action. Conversely, Beclin-1 is upregulated in cancer stem cells (CSCs), portending a role in cancer recurrence, and highlighting this molecule as an intriguing molecular target for the treatment of CSCs. Many aspects of Beclin-1's biological effects remain to be studied. The consequences of these BLAST searches on the molecular evolution of Beclin-1, and the eukaryotic branches of the tree of life, are discussed here in greater detail with future inquiry focused upon protist taxa. Also in this review, the effects of Beclin-1 on tumor suppression and cancer malignancy are discussed. Beclin-1 holds significant promise for the development of novel targeted cancer therapeutics and is anticipated to lead to a many advances in our understanding of eukaryotic evolution, multicellularity, and even the treatment of CSCs in the coming decades.

Exploring the Cultivable Ectocarpus Microbiome.

Coastal areas form the major habitat of brown macroalgae, photosynthetic multicellular eukaryotes that have great ecological value and industrial potential. Macroalgal growth, development, and physiology are influenced by the microbial community they accommodate. Studying the algal microbiome should thus increase our fundamental understanding of algal biology and may help to improve culturing efforts. Currently, a freshwater strain of the brown macroalga Ectocarpus subulatus is being developed as a model organism for brown macroalgal physiology and algal microbiome studies. It can grow in high and low salinities depending on which microbes it hosts. However, the molecular mechanisms involved in this process are still unclear. Cultivation of Ectocarpus-associated bacteria is the first step toward the development of a model system for in vitro functional studies of brown macroalgal–bacterial interactions during abiotic stress. The main aim of the present study is thus to provide an extensive collection of cultivable E. subulatus-associated bacteria. To meet the variety of metabolic demands of Ectocarpus-associated bacteria, several isolation techniques were applied, i.e., direct plating and dilution-to-extinction cultivation techniques, each with chemically defined and undefined bacterial growth media. Algal tissue and algal growth media were directly used as inoculum, or they were pretreated with antibiotics, by filtration, or by digestion of algal cell walls. In total, 388 isolates were identified falling into 33 genera (46 distinct strains), of which Halomonas (Gammaproteobacteria), Bosea (Alphaproteobacteria), and Limnobacter (Betaproteobacteria) were the most abundant. Comparisons with 16S rRNA gene metabarcoding data showed that culturability in this study was remarkably high (∼50%), although several cultivable strains were not detected or only present in extremely low abundance in the libraries. These undetected bacteria could be considered as part of the rare biosphere and they may form the basis for the temporal changes in the Ectocarpus microbiome.

Carbonaceous biosignatures of the earliest putative macroscopic multicellular eukaryotes from 1630 Ma Tuanshanzi Formation, north China

The Paleo- and Mesoproterozoic fossil record of multicellular eukaryotes is scarce but extremely important in studying the evolution of life in the Precambrian Era. Typically, fossils heralded as ‘multicellular eukaryotes’ that are older than the Ediacaran are met with controversy. To confront such debates, we investigate the chemical, isotopic, and molecular structural characteristics of organic matter from carbonaceous compressions in the 1630 Ma Tuanshanzi Formation in northern China, some of the earliest putative macroscopic multicellular eukaryote fossils (Zhu and Chen, 1995). The large-size and relative complexity of these fossils and similar remains from the 1.56 Ga Gaoyuzhuang Formation have led to their interpretation as eukaryotes. Raman spectral parameters give an estimated peak-metamorphic temperature TMax in the range of 202–286 °C, confirming the good preservation of the organic remains. Two-dimensional Raman maps of the carbonaceous compressions show ultrastructural variations that suggest diverse subcellular compounds being consistent with multicellular eukaryotes. The organic matter has carbon isotopic composition δ13Corg-SIMS between −45.3 and −32.2‰, and a branching index of carbon chain measured by the micro-FTIR spectral parameter R3/2 between 0.17 and 0.31. Together with their large-size and morphology, the isotopic, geochemical and ultrastructural data supports an interpretation of the Tuanshanzi Formation carbonaceous compressions as derived from phototrophic, multicellular eukaryotic algae. Our data support the early evolution of macroscopic multicellular eukaryotes in the sulfidic and low-oxygen conditions that prevailed in the Paleo- and Mesoproterozoic oceans.

The thermodynamic efficiency of computations made in cells across the range of life.

Biological organisms must perform computation as they grow, reproduce and evolve. Moreover, ever since Landauer's bound was proposed, it has been known that all computation has some thermodynamic cost-and that the same computation can be achieved with greater or smaller thermodynamic cost depending on how it is implemented. Accordingly an important issue concerning the evolution of life is assessing the thermodynamic efficiency of the computations performed by organisms. This issue is interesting both from the perspective of how close life has come to maximally efficient computation (presumably under the pressure of natural selection), and from the practical perspective of what efficiencies we might hope that engineered biological computers might achieve, especially in comparison with current computational systems. Here we show that the computational efficiency of translation, defined as free energy expended per amino acid operation, outperforms the best supercomputers by several orders of magnitude, and is only about an order of magnitude worse than the Landauer bound. However, this efficiency depends strongly on the size and architecture of the cell in question. In particular, we show that the useful efficiency of an amino acid operation, defined as the bulk energy per amino acid polymerization, decreases for increasing bacterial size and converges to the polymerization cost of the ribosome. This cost of the largest bacteria does not change in cells as we progress through the major evolutionary shifts to both single- and multicellular eukaryotes. However, the rates of total computation per unit mass are non-monotonic in bacteria with increasing cell size, and also change across different biological architectures, including the shift from unicellular to multicellular eukaryotes.This article is part of the themed issue 'Reconceptualizing the origins of life'.

Evolution and adaptation of single-pass transmembrane proteins

A comparative analysis of 6039 single-pass (bitopic) membrane proteins from six evolutionarily distant organisms was performed based on data from the Membranome database. The observed repertoire of bitopic proteins is significantly enlarged in eukaryotic cells and especially in multicellular organisms due to the diversification of enzymes, emergence of proteins involved in vesicular trafficking, and expansion of receptors, structural, and adhesion proteins. The majority of bitopic proteins in multicellular organisms are located in the plasma membrane (PM) and involved in cell communication. Bitopic proteins from different membranes significantly diverge in terms of their biological functions, size, topology, domain architecture, physical properties of transmembrane (TM) helices and propensity to form homodimers. Most proteins from eukaryotic PM and endoplasmic reticulum (ER) have the N-out topology. The predicted lengths of TM helices and hydrophobic thicknesses, stabilities and hydrophobicities of TM α-helices are the highest for proteins from eukaryotic PM, intermediate for proteins from prokaryotic cells, ER and Golgi apparatus, and lowest for proteins from mitochondria, chloroplasts, and peroxisomes. Tyr and Phe residues accumulate at the cytoplasmic leaflet of PM and at the outer leaflet of membranes of bacteria, Golgi apparatus, and nucleus. The propensity for dimerization increases from unicellular to multicellular eukaryotes, from enzymes to receptors, and from intracellular membrane proteins to PM proteins. More than half of PM proteins form homodimers with a 2:1 ratio of right-handed to left-handed helix packing arrangements. The inverse ratio (1:2) was observed for dimers from the ER, Golgi and vesicles.

Retrograde nuclear transport from the cytoplasm is required for tRNATyr maturation in T. brucei

ABSTRACTRetrograde transport of tRNAs from the cytoplasm to the nucleus was first described in Saccharomyces cerevisiae and most recently in mammalian systems. Although the function of retrograde transport is not completely clear, it plays a role in the cellular response to changes in nutrient availability. Under low nutrient conditions tRNAs are sent from the cytoplasm to nucleus and presumably remain in storage there until nutrient levels improve. However, in S. cerevisiae tRNA retrograde transport is constitutive and occurs even when nutrient levels are adequate. Constitutive transport is important, at least, for the proper maturation of tRNAPhe, which undergoes cytoplasmic splicing, but requires the action of a nuclear modification enzyme that only acts on a spliced tRNA. A lingering question in retrograde tRNA transport is whether it is relegated to S. cerevisiae and multicellular eukaryotes or alternatively, is a pathway with deeper evolutionary roots. In the early branching eukaryote Trypanosoma brucei, tRNA splicing, like in yeast, occurs in the cytoplasm. In the present report, we have used a combination of cell fractionation and molecular approaches that show the presence of significant amounts of spliced tRNATyr in the nucleus of T. brucei. Notably, the modification enzyme tRNA-guanine transglycosylase (TGT) localizes to the nucleus and, as shown here, is not able to add queuosine (Q) to an intron-containing tRNA. We suggest that retrograde transport is partly the result of the differential intracellular localization of the splicing machinery (cytoplasmic) and a modification enzyme, TGT (nuclear). These findings expand the evolutionary distribution of retrograde transport mechanisms to include early diverging eukaryotes, while highlighting its importance for queuosine biosynthesis.

Proteogenomics Gets onto the Regulation of mRNA Decoding and Translation into Protein.

Proteogenomics, the integrative analysis of the proteome and the genome, increasingly provides protein-level insights about the regulation of gene expression and protein translation. Armengaud et al. (Proteomics 2017, 17, 1700211) nicely illustrate this trend with the first in-depth proteomic analysis of the eukaryotic and unicellular intestinal parasite Blastocystis sp. Not only this work constitutes an important milestone toward the proteogenomics profile of this human pathogen, but also it demonstrates at the protein level the occurrence of a specific mechanism of mRNA decoding. GU-rich motifs located downstream of mRNA polyadenylation sites create termination codons that ultimately result in the synthesis of proteins with lower molecular weight than predicted from gene sequence. Thus, the scope of proteogenomics now extends to the regulation of mRNA translation into proteins, providing a proof of concept for future studies in multicellular eukaryotes such as humans and plants.

Photo-safety assessment for cosmetics based on in vitro tests

Infliction of DNA damage initiates a complex cellular reaction – the DNA damage response – that involves both signaling and DNA repair networks with many redundancies and parallel pathways. Here, we reveal the three strategies that the simple multicellular eukaryote, C. elegans, uses to deal with DNA damage induced by light. Separately inactivating repair or replicative bypass of photo-lesions results in cellular hypersensitivity towards UV-light, but impeding repair of replication associated DNA breaks does not. Yet, we observe an unprecedented synergistic relationship when these pathways are inactivated in combination. C. elegans mutants that lack nucleotide excision repair (NER), translesion synthesis (TLS) and alternative end joining (altEJ) grow undisturbed in the dark, but become sterile when grown in light. Even exposure to very low levels of normal daylight impedes animal growth. We show that NER and TLS operate to suppress the formation of lethal DNA breaks that require polymerase theta-mediated end joining (TMEJ) for their repair. Our data testifies to the enormous genotoxicity of light and to the demand of multiple layers of protection against an environmental threat that is so common.

An eukaryote-bearing microbiota from the early mesoproterozoic Gaoyuzhuang Formation, Tianjin, China and its significance

On the basis of expanded documentation of complex fossils, early Mesoproterozoic has already been proven asan important Era for eukaryotic evolution. In order to portray the biological community of this critical era, we studied a new silicified microbiota from the ∼1560Ma Gaoyuzhuang Formation in the classic Jixian section, Tianjin, China. In total, eighteen species have been recognized, four species have been identified informally and five species have been identified in open nomenclature. Similar to other Proterozoic microbial mat biota, the new microbiota is dominated by cyanobacteria filaments and coccoids as well. Potential eukaryotic microfossils, such as ornamented coccoids, filaments with flanges and terminal cell, were firstly recovered. Amongst them, filaments with flanges and conidia-like terminal cell probably were the earliest unidirectional growing multi-cellular organisms as well as the earliest phylogeny-resolved multicellular eukaryotes. Combined with increasing records of Proterozoic eukaryotes, these microfossils indicated that eukaryotes have evolved into a new level in Early Mesoproterozoic.

ATAD3 proteins: brokers of a mitochondria-endoplasmic reticulum connection in mammalian cells.

In yeast, a sequence of physical and genetic interactions termed the endoplasmic reticulum (ER)-mitochondria organizing network (ERMIONE) controls mitochondria-ER interactions and mitochondrial biogenesis. Several functions that characterize ERMIONE complexes are conserved in mammalian cells, suggesting that a similar tethering complex must exist in metazoans. Recent studies have identified a new family of nuclear-encoded ATPases associated with diverse cellular activities (AAA+-ATPase) mitochondrial membrane proteins specific to multicellular eukaryotes, called the ATPase family AAA domain-containing protein 3 (ATAD3) proteins (ATAD3A and ATAD3B). These proteins are crucial for normal mitochondrial-ER interactions and lie at the heart of processes underlying mitochondrial biogenesis. ATAD3A orthologues have been studied in flies, worms, and mammals, highlighting the widespread importance of this gene during embryonic development and in adulthood. ATAD3A is a downstream effector of target of rapamycin (TOR) signalling in Drosophila and exhibits typical features of proteins from the ERMIONE-like complex in metazoans. In humans, mutations in the ATAD3A gene represent a new link between altered mitochondrial-ER interaction and recognizable neurological syndromes. The primate-specific ATAD3B protein is a biomarker of pluripotent embryonic stem cells. Through negative regulation of ATAD3A function, ATAD3B supports mitochondrial stemness properties.

And yet, it moves: nuclear and chromatin dynamics of a heterochromatic double-strand break.

Heterochromatin is mostly composed of repeated DNA sequences prone to aberrant recombination. How cells maintain the stability of these sequences during double-strand break (DSB) repair has been a long-standing mystery. Studies in Drosophila cells revealed that faithful homologous recombination repair of heterochromatic DSBs relies on the striking relocalization of repair sites to the nuclear periphery before Rad51 recruitment and repair progression. Here, we summarize our current understanding of this response, including the molecular mechanisms involved, and conserved pathways in mammalian cells. We will highlight important similarities with pathways identified in budding yeast for repair of other types of repeated sequences, including rDNA and short telomeres. We will also discuss the emerging role of chromatin composition and regulation in heterochromatin repair progression. Together, these discoveries challenged previous assumptions that repair sites are substantially static in multicellular eukaryotes, that heterochromatin is largely inert in the presence of DSBs, and that silencing and compaction in this domain are obstacles to repair.This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.

Transitions between marine and freshwater environments provide new clues about the origins of multicellular plants and algae.

Marine-freshwater and freshwater-marine transitions have been key events in the evolution of life, and most major groups of organisms have independently undergone such events at least once in their history. Here, we first compile an inventory of bidirectional freshwater and marine transitions in multicellular photosynthetic eukaryotes. While green and red algae have mastered multiple transitions in both directions, brown algae have colonized freshwater on a maximum of six known occasions, and angiosperms have made the transition to marine environments only two or three times. Next, we review the early evolutionary events leading to the colonization of current habitats. It is commonly assumed that the conquest of land proceeded in a sequence from marine to freshwater habitats. However, recent evidence suggests that early photosynthetic eukaryotes may have arisen in subaerial or freshwater environments and only later colonized marine environments as hypersaline oceans were diluted to the contemporary level. Although this hypothesis remains speculative, it is important to keep these alternative scenarios in mind when interpreting the current habitat distribution of plants and algae. Finally, we discuss the roles of structural and functional adaptations of the cell wall, reactive oxygen species scavengers, osmoregulation, and reproduction. These are central for acclimatization to freshwater or to marine environments. We observe that successful transitions appear to have occurred more frequently in morphologically simple forms and conclude that, in addition to physiological studies of euryhaline species, comparative studies of closely related species fully adapted to one or the other environment are necessary to better understand the adaptive processes.

Conserved nucleolar stress at the onset of cell death.

Cell death pervasiveness among multicellular eukaryotes suggested that some core steps of cell death may be conserved. This could be addressed by comparing the course of cell death in organisms belonging to distinct eukaryotic kingdoms. A search for early cell death events in a protist revealed nucleolar disorganization similar to the nucleolar stress often reported in dying animal cells. This indicated a conserved role for the nucleolus at the onset of eukaryotic cell death and leads one to consider the course of cell death as a succession of unequally conserved modules.

Superorganismality and caste differentiation as points of no return: how the major evolutionary transitions were lost in translation.

More than a century ago, William Morton Wheeler proposed that social insect colonies can be regarded as superorganisms when they have morphologically differentiated reproductive and nursing castes that are analogous to the metazoan germ-line and soma. Following the rise of sociobiology in the 1970s, Wheeler's insights were largely neglected, and we were left with multiple new superorganism concepts that are mutually inconsistent and uninformative on how superorganismality originated. These difficulties can be traced to the broadened sociobiological concept of eusociality, which denies that physical queen-worker caste differentiation is a universal hallmark of superorganismal colonies. Unlike early evolutionary naturalists and geneticists such as Weismann, Huxley, Fisher and Haldane, who set out to explain the acquisition of an unmated worker caste, the goal of sociobiology was to understand the evolution of eusociality, a broad-brush convenience category that covers most forms of cooperative breeding. By lumping a diverse spectrum of social systems into a single category, and drawing attention away from the evolution of distinct quantifiable traits, the sociobiological tradition has impeded straightforward connections between inclusive fitness theory and the major evolutionary transitions paradigm for understanding irreversible shifts to higher organizational complexity. We evaluate the history by which these inconsistencies accumulated, develop a common-cause approach for understanding the origins of all major transitions in eukaryote hierarchical complexity, and use Hamilton's rule to argue that they are directly comparable. We show that only Wheeler's original definition of superorganismality can be unambiguously linked to irreversible evolutionary transitions from context-dependent reproductive altruism to unconditional differentiation of permanently unmated castes in the ants, corbiculate bees, vespine wasps and higher termites. We argue that strictly monogamous parents were a necessary, albeit not sufficient condition for all transitions to superorganismality, analogous to single-zygote bottlenecking being a necessary but not sufficient condition for the convergent origins of complex soma across multicellular eukaryotes. We infer that conflict reduction was not a necessary condition for the origin of any of these major transitions, and conclude that controversies over the status of inclusive fitness theory primarily emanate from the arbitrarily defined sociobiological concepts of superorganismality and eusociality, not from the theory itself.

Fluoride export (FEX) proteins from fungi, plants and animals are 'single barreled' channels containing one functional and one vestigial ion pore.

The fluoride export protein (FEX) in yeast and other fungi provides tolerance to fluoride (F-), an environmentally ubiquitous anion. FEX efficiently eliminates intracellular fluoride that otherwise would accumulate at toxic concentrations. The FEX homolog in bacteria, Fluc, is a ‘double-barreled’ channel formed by dimerization of two identical or similar subunits. FEX in yeast and other eukaryotes is a monomer resulting from covalent fusion of the two subunits. As a result, both potential fluoride pores are created from different parts of the same protein. Here we identify FEX proteins from two multicellular eukaryotes, a plant Arabidopsis thaliana and an animal Amphimedon queenslandica, by demonstrating significant fluoride tolerance when these proteins are heterologously expressed in the yeast Saccharomyces cerevisiae. Residues important for eukaryotic FEX function were determined by phylogenetic sequence alignment and functional analysis using a yeast growth assay. Key residues of the fluoride channel are conserved in only one of the two potential fluoride-transporting pores. FEX activity is abolished upon mutation of residues in this conserved pore, suggesting that only one of the pores is functional. The same topology is conserved for the newly identified FEX proteins from plant and animal. These data suggest that FEX family of fluoride channels in eukaryotes are ‘single-barreled’ transporters containing one functional pore and a second non-functional vestigial remnant of a homologous gene fusion event.

Transient deep-water oxygenation in the early Cambrian Nanhua Basin, South China

Many late Neoproterozoic to early Cambrian fossils of multicellular eukaryotes, including those of benthic animals, are found preserved under anoxic and even euxinic bottom-water conditions, which is contradictory to the consensus that oxygen is essential to eukaryotes. To investigate this conundrum, we conducted an integrated study of iron speciation, redox-sensitive trace elements, and Mo isotopes (δ98Mo) on the black shale interval of the lower Cambrian Hetang Formation (∼535–521Ma) at Lantian, South China, in which benthic sponge fossils are abundant in the lower member (LM) but absent in the upper member (UM). Iron speciation data point to uniformly anoxic-ferruginous conditions in the LM and euxinic conditions in the UM, whereas the trace-element and δ98Mo data show greater secular variation in redox conditions. The LM shows higher mean trace element concentrations (Mo: 108ppm, U: 36ppm, V: 791ppm) and lower and more variable δ98Mo (+0.13 to +1.76‰) relative to the UM (Mo: 45ppm, U: 18ppm, V: 265ppm, δ98Mo: +1.59 to +1.67‰), and ratios of redox-sensitive trace element concentrations to total organic carbon are significantly more variable and higher on average in the LM relative to the UM. The appearance of sponge fossils and lower δ98Mo values correlate strongly with gray (i.e., lighter-colored) layers in the LM. These patterns can best be interpreted as recording mainly euxinic conditions throughout deposition of the study units, with more intense background euxinia in the LM relative to the UM, but also with frequent transient oxygenation events in the LM that do not appear in the UM. The transient oxygenation events of the LM led to the initial colonization of the deep Nanhua Basin by sponges, and the termination of these events in the UM caused sponge faunas to disappear until a general rise in O2 levels later in the Cambrian permitted their return to deeper-water habitats. Our study also illustrates that multiple geochemical and paleobiological proxies exhibit different responses in ‘poikiloredox’ environments (i.e., characterized by small-scale spatial and high-frequency temporal variations), which can lead to apparent contradictions between metazoan fossil occurrences and their inferred watermass redox conditions.

Combined loss of three DNA damage response pathways renders C. elegans intolerant to light

Infliction of DNA damage initiates a complex cellular reaction – the DNA damage response – that involves both signaling and DNA repair networks with many redundancies and parallel pathways. Here, we reveal the three strategies that the simple multicellular eukaryote, C. elegans, uses to deal with DNA damage induced by light. Separately inactivating repair or replicative bypass of photo-lesions results in cellular hypersensitivity towards UV-light, but impeding repair of replication associated DNA breaks does not. Yet, we observe an unprecedented synergistic relationship when these pathways are inactivated in combination. C. elegans mutants that lack nucleotide excision repair (NER), translesion synthesis (TLS) and alternative end joining (altEJ) grow undisturbed in the dark, but become sterile when grown in light. Even exposure to very low levels of normal daylight impedes animal growth. We show that NER and TLS operate to suppress the formation of lethal DNA breaks that require polymerase theta-mediated end joining (TMEJ) for their repair. Our data testifies to the enormous genotoxicity of light and to the demand of multiple layers of protection against an environmental threat that is so common.

Human eIF3: from 'blobology' to biological insight.

Translation in eukaryotes is highly regulated during initiation, a process impacted by numerous readouts of a cell's state. There are many cases in which cellular messenger RNAs likely do not follow the canonical ‘scanning’ mechanism of translation initiation, but the molecular mechanisms underlying these pathways are still being uncovered. Some RNA viruses such as the hepatitis C virus use highly structured RNA elements termed internal ribosome entry sites (IRESs) that commandeer eukaryotic translation initiation, by using specific interactions with the general eukaryotic translation initiation factor eIF3. Here, I present evidence that, in addition to its general role in translation, eIF3 in humans and likely in all multicellular eukaryotes also acts as a translational activator or repressor by binding RNA structures in the 5′-untranslated regions of specific mRNAs, analogous to the role of the mediator complex in transcription. Furthermore, eIF3 in multicellular eukaryotes also harbours a 5′ 7-methylguanosine cap-binding subunit—eIF3d—which replaces the general cap-binding initiation factor eIF4E in the translation of select mRNAs. Based on results from cell biological, biochemical and structural studies of eIF3, it is likely that human translation initiation proceeds through dozens of different molecular pathways, the vast majority of which remain to be explored.This article is part of the themed issue ‘Perspectives on the ribosome’.