DNA methylation differs extensively between strains of the same geographical origin and changes with age in Daphnia magna

Background Patterns of methylation influence lifespan, but methylation and lifespan may also depend on diet, or differ between genotypes. Prior to this study, interactions between diet and genotype have not been explored together to determine their influence on methylation. The invertebrate Daphnia magna is an excellent choice for testing the epigenetic response to the environment: parthenogenetic offspring are identical to their siblings (making for powerful genetic comparisons), they are relatively short lived and have well-characterised inter-strain life-history trait differences. We performed a survival analysis in response to caloric restriction and then undertook a 47-replicate experiment testing the DNA methylation response to ageing and caloric restriction of two strains of D. magna. Results Methylated cytosines (CpGs) were most prevalent in exons two to five of gene bodies. One strain exhibited a significantly increased lifespan in response to caloric restriction, but there was no effect of food-level CpG methylation status. Inter-strain differences dominated the methylation experiment with over 15,000 differently methylated CpGs. One gene, Me31b, was hypermethylated extensively in one strain and is a key regulator of embryonic expression. Sixty-one CpGs were differentially methylated between young and old individuals, including multiple CpGs within the histone H3 gene, which were hypermethylated in old individuals. Across all age-related CpGs, we identified a set that are highly correlated with chronological age. Conclusions Methylated cytosines are concentrated in early exons of gene sequences indicative of a directed, non-random, process despite the low overall DNA methylation percentage in this species. We identify no effect of caloric restriction on DNA methylation, contrary to our previous results, and established impacts of caloric restriction on phenotype and gene expression. We propose our approach here is more robust in invertebrates given genome-wide CpG distributions. For both strain and ageing, a single gene emerges as differentially methylated that for each factor could have widespread phenotypic effects. Our data showed the potential for an epigenetic clock at a subset of age positions, which is exciting but requires confirmation

Hyperevolution of trypanosome Variant Surface Glycoprotein genes

The African sleeping sickness parasite Trypanosoma brucei evades the immune system of its mammalian host by periodically switching the variant surface glycoprotein (VSG) that forms its cell-surface coat. This process of antigenic variation utilises a large archive of VSG genes, which are primarily subtelomeric and appear to evolve rapidly. Subtelomeres are the location of multi-member, variable gene families in many organisms, and often seem to have an elevated rate of mutation. The VSG archive is a particularly striking example of an organism taking advantage of this environment to promote hyperevolution. The aim of this project was to investigate the changes that occur in VSG evolution. In collaboration with researchers at the Sanger Institute, genomes from two time-separated isolates of the same trypanosome strain were sequenced and assembled. The quality of the genome assemblies was assessed, and the genomes concluded to be of sufficient quality for further analysis. Chromosome core genes and VSG N-terminal domain (NTD) genes and pseudogenes were annotated in each genome, and mutations between the genomes in each gene were catalogued. VSG NTDs had a significantly higher mutation frequency than core genes, and the specific patterns of mutations differed significantly between the two genome regions. These results together implied that VSG are subject to different mutational processes from core genes. However, mutation frequency did not appear to differ between VSG NTDs and other subtelomeric sequence, indicating that it is the subtelomeres in general that are subject to elevated mutational activity. Further examination of the VSG NTDs within each new genome reinforced published observations in the reference genome strain VSG archive of extensive substructuring and abundance of pseudogenes. Finally, to address the question of which mechanisms may be involved in elevating the mutation rate in subtelomeres, an attempt was made to characterise two members of a gene family predicted to encode error-prone lesion bypass DNA polymerases, a class of enzymes that have been suggested to have a role in the systematic generation of mutations. Such results as were obtained suggested that the genes examined may not encode active polymerases, and the results did not provide any evidence for a role for these polymerases in VSG hyperevolution. Overall, however, the project has uncovered considerable detail of how hypermutation proceeds in this highly variable gene family

Origin of the human malaria parasite Plasmodium vivax

The geographic origin of Plasmodium vivax, a leading cause of human malaria, has been the subject of much speculation. Here we review the evolutionary history of P. vivax and P. vivax-like parasites in humans and non-human primates on three continents, providing overwhelming evidence for an African origin. This conclusion is consistent with recent reports showing that Duffy-negative humans in Africa are, in fact, susceptible to P. vivax, with parasites invading Duffy-antigen-expressing erythroid precursors. Thus, the African origin of P. vivax not only explains the distribution of the Duffy-negative genotype but also provides new insight into the history and status of P. vivax malaria in Africa and efforts geared toward its eradication.</p

Unusually Divergent Ubiquitin Genes and Proteins in Plasmodium Species

Ubiquitin is an extraordinarily highly conserved 76 amino acid protein encoded by three different types of gene, where the primary translation products are fusions either of ubiquitin with one of two ribosomal proteins (RPs) or of multiple ubiquitin monomers from head to tail. Here, we investigate the evolution of ubiquitin genes in mammalian malaria parasites (Plasmodium species). The ubiquitin encoded by the RPS27a fusion gene is highly divergent, as previously found in a variety of protists. However, we also find that two other forms of divergent ubiquitin sequence, each previously thought to be extremely rare, have arisen recently during the divergence of Plasmodium subgenera. On two occasions, in two distinct lineages, the ubiquitin encoded by the RPL40 fusion gene has rapidly diverged. In addition, in one of these lineages, the polyubiquitin genes have undergone a single codon insertion, previously considered a unique feature of Rhizaria. There has been disagreement whether the multiple ubiquitin coding repeats within a genome exhibit concerted evolution or undergo a birth-and-death process; the Plasmodium ubiquitin genes show clear signs of concerted evolution, including the spread of this codon insertion to multiple repeats within the polyubiquitin gene.</p

Simultaneous initiation of radical and cationic polymerization reactions using the "G1" copper complex as photoredox catalyst: Applications of free radical/cationic hybrid photopolymerization in the composites and

WOS:000469902800007This investigation presents the use of a photoredox catalyst "G1" as a photoinitiating system for free radical/cationic hybrid polymerization under mild irradiation conditions. The G1 system (G1/iodonium salt/N-vinylcarbazole), can simultaneously initiate the free radical and cationic polymerization reactions upon exposure to a visible (405 nm) light from a Light Emitting Diode (LED) source. The multicomponent G1 system is able to simultaneously generate radical and cationic species through a catalytic photoredox process. The curing of thin samples (25 mu m), thick samples (1.4 mm) as well as the manufacture of hybrid system/glass fibers composites ( 2 to 4 mm thickness) was realized and the influence of the ratio of cationic/radical monomer blends on the polymerization kinetics was studied. The use of G1 in visible light photoinitiating system for the access to composites and 3D printing experiments was particularly outlined. G1 was also shown to have low levels of migration from the cured materials. When compared to reference materials ("F1", a similar copper complex and an anthracene derivative, dibutoxy anthracene), G1 showed better polymerization efficiency. The initiation efficiency was investigated through the real-time Fourier transform infrared (RT-FTIR) spectroscopy and optical pyrometry. Dynamical Mechanical Analysis has been used to determine the glass temperature transition of the cured hybrid system as a complementary technique

The effect of breached relay ramp structures on deep‐lacustrine sedimentary systems

Fault relay ramps are important sediment delivery points along rift margins and often provide persistent flow pathways in deepwater sedimentary basins. They form as tilted rock volumes between en-echelon fault segments, which become modified through progressive deformation, and may develop through-going faults that ‘breach’ the relay ramp. It is well established that hinterland drainage (fluvial/alluvial systems) is greatly affected by the presence of relay ramps at basin margins. However, the impact on deepwater (deep-marine/lacustrine) subaqueous sediment gravity flow processes, particularly by breached relay ramps, is less well documented. To better evaluate the complex geology of breached relay settings, this study examines a suite of high-quality subsurface data from the Early Cretaceous deep-lacustrine North Falkland Basin (NFB). The Isobel Embayment breached relay-ramp, an ideal example, formed during the syn-rift and was later covered by a thick transitional and early post-rift succession. Major transitional and early post-rift fan systems are observed to have consistently entered the basin at the breached relay location, directed through a significant palaeo-bathymetric low associated with the lower, abandoned ramp of the structure. More minor systems also entered the basin across the structure-bounding fault to the north. Reactivation of basin-bounding faults is shown by the introduction of new point sources along its extent. This study shows the prolonged influence of margin-located relay ramps on sedimentary systems from syn-rift, transitional and into the early post-rift phase. It suggests that these structures can become reactivated during post-rift times, providing continued control on deposition and sourcing of overlying sedimentary systems. Importantly, breached relays exert control on fan distribution, characterised by laterally extensive lobes sourced by widespread feeder systems, and hanging walls settings by small-scale lobes, with small, often line-sourced feeders. Further characterising the likely sandstone distribution in these structurally complex settings is important as these systems often form attractive hydrocarbon reservoirs

Hybrid event bed character and distribution in the context of ancient deep‐lacustrine fan models

Hybrid event beds are texturally and compositionally-diverse deposits preserved within deepwater settings. They are deposited by flows exhibiting ‘mixed behaviour’, forming complex successions of sandstone and mudstone, which are often challenging to predict. Hybrid event beds are documented in deep-marine settings, where they have been thoroughly characterized, and are well-known as effective fluid transmissibility barriers and baffles in reservoirs. By comparison, there are far-fewer studies of hybrid event beds from deep-lacustrine settings, where their character and distribution remains relatively under-explored. In order to provide insights into these deposits, this study presents the detailed analysis of three-dimensional seismic data, wireline logs and core from a series of ancient deep-lacustrine fan systems in the North Falkland Basin. Results confirm that deep-lacustrine hybrid event beds comprise the same idealized sequence of the ‘H1–H5’ divisions. However, in this study H3 ‘debrite’ units can be sub-divided into ‘H3a–H3c’, based on: sharp or erosional intra-H3 contacts, bulk lithology, mud-content and discrete sedimentary textures. This study interprets the H3a–H3c sub-units as the products of multiple flow components formed through significant rearward longitudinal flow transformation processes, during the emplacement of a single hybrid event bed. Hybrid event beds are observed within lobe fringes, where flow types, energies, and transport mechanisms diversify as a result of flow transformation. The temporal context of hybrid event bed occurrences is considered in relation to stages of fan evolution, including: the Initiation; Growth (I); Growth (II); By-pass; Abandonment; and Termination phases. Hybrid event beds are mainly found in either the initiation phase where flow interaction and erosion of initial substrates promoted mixed flow behaviour, or in the abandonment phase as facies belt retreated landward. The results of this study have important implications in terms of flow processes of hybrid event bed emplacement, in particular sub-division of the H3 unit, as well as the prediction of hybrid event bed occurrence and character within ancient deep-lacustrine fan settings, in-general

Multigenomic Delineation of Plasmodium Species of the Laverania Subgenus Infecting Wild-living Chimpanzees and Gorillas

Plasmodium falciparum, the major cause of malaria morbidity and mortality worldwide, is only distantly related to other human malaria parasites and has thus been placed in a separate subgenus, termed Laverania. Parasites morphologically similar to P. falciparum have been identified in African apes, but only one other Laverania species, Plasmodium reichenowi from chimpanzees, has been formally described. Although recent studies have pointed to the existence of additional Laverania species, their precise number and host associations remain uncertain, primarily because of limited sampling and a paucity of parasite sequences other than from mitochondrial DNA. To address this, we used limiting dilution polymerase chain reaction to amplify additional parasite sequences from a large number of chimpanzee and gorilla blood and fecal samples collected at two sanctuaries and 30 field sites across equatorial Africa. Phylogenetic analyses of more than 2,000 new sequences derived from the mitochondrial, nuclear, and apicoplast genomes revealed six divergent and well-supported clades within the Laverania parasite group. Although two of these clades exhibited deep subdivisions in phylogenies estimated from organelle gene sequences, these sublineages were geographically defined and not present in trees from four unlinked nuclear loci. This greatly expanded sequence data set thus confirms six, and not seven or more, ape Laverania species, of which P. reichenowi, Plasmodium gaboni, and Plasmodium billcollinsi only infect chimpanzees, whereas Plasmodium praefalciparum, Plasmodium adleri, and Pladmodium blacklocki only infect gorillas. The new sequence data also confirm the P. praefalciparum origin of human P. falciparum