Ancestral population genomics

The full genomes of several closely related species are now available, opening an emerging field of investigation borrowing both from population genetics and phylogenetics. Providing we can properly model sequence evolution within populations undergoing speciation events, this resource enables us to estimate key population genetics parameters, such as ancestral population sizes and split times. Furthermore, we can enhance our understanding of the recombination process and investigate various selective forces. We discuss the basic speciation models for closely related species, including the isolation and isolation-with-migration models. A major point in our discussion is that only a few complete genomes contain much information about the whole population. The reason being that recombination unlinks genomic regions, and therefore a few genomes contain many segments with distinct histories. The challenge of population genomics is to decode this mosaic of histories in order to infer scenarios of demography and selection. We survey different approaches for understanding ancestral species from analyses of genomic data from closely related species. In particular, we emphasize core assumptions and working hypothesis. Finally, we discuss computational and statistical challenges that arise in the analysis of population genomics data sets

The structural determinants of intra-protein compensatory substitutions

Compensatory substitutions happen when one mutation is advantageously selected because it restores the loss of fitness induced by a previous deleterious mutation. How frequent such mutations occur in evolution and what is the structural and functional context permitting their emergence remain open questions. We built an atlas of intra-protein compensatory substitutions using a phylogenetic approach and a dataset of 1,630 bacterial protein families for which high-quality sequence alignments and experimentally derived protein structures were available. We identified more than 51,000 positions coevolving by the mean of predicted compensatory mutations. Using the evolutionary and structural properties of the analyzed positions, we demonstrate that compensatory mutations are scarce (typically only a few in the protein history) but widespread (the majority of proteins experienced at least one). Typical coevolving residues are evolving slowly, are located in the protein core outside secondary structure motifs, and are more often in contact than expected by chance, even after accounting for their evolutionary rate and solvent exposure. An exception to this general scheme is residues coevolving for charge compensation, which are evolving faster than noncoevolving sites, in contradiction with predictions from simple coevolutionary models, but similar to stem pairs in RNA. While sites with a significant pattern of coevolution by compensatory mutations are rare, the comparative analysis of hundreds of structures ultimately permits a better understanding of the link between the three-dimensional structure of a protein and its fitness landscape

Variation of the adaptive substitution rate between species and within genomes

The importance of adaptive mutations in molecular evolution is extensively debated. Recent developments in population genomics allow inferring rates of adaptive mutations by fitting a distribution of fitness effects to the observed patterns of polymorphism and divergence at sites under selection and sites assumed to evolve neutrally. Here, we summarize the current state-of-the-art of these methods and review the factors that affect the molecular rate of adaptation. Several studies have reported extensive cross-species variation in the proportion of adaptive amino-acid substitutions (α) and predicted that species with larger effective population sizes undergo less genetic drift and higher rates of adaptation. Disentangling the rates of positive and negative selection, however, revealed that mutations with deleterious effects are the main driver of this population size effect and that adaptive substitution rates vary comparatively little across species. Conversely, rates of adaptive substitution have been documented to vary substantially within genomes. On a genome-wide scale, gene density, recombination and mutation rate were observed to play a role in shaping molecular rates of adaptation, as predicted under models of linked selection. At the gene level, it has been reported that the gene functional category and the macromolecular structure substantially impact the rate of adaptive mutations. Here, we deliver a comprehensive review of methods used to infer the molecular adaptive rate, the potential drivers of adaptive evolution and how positive selection shapes molecular evolution within genes, across genes within species and between species

Strong evidence for the adaptive walk model of gene evolution in Drosophila and Arabidopsis

Understanding the dynamics of species adaptation to their environments has long been a central focus of the study of evolution. Theories of adaptation propose that populations evolve by “walking” in a fitness landscape. This “adaptive walk” is characterised by a pattern of diminishing returns, where populations further away from their fitness optimum take larger steps than those closer to their optimal conditions. Hence, we expect young genes to evolve faster and experience mutations with stronger fitness effects than older genes because they are further away from their fitness optimum. Testing this hypothesis, however, constitutes an arduous task. Young genes are small, encode proteins with a higher degree of intrinsic disorder, are expressed at lower levels, and are involved in species-specific adaptations. Since all these factors lead to increased protein evolutionary rates, they could be masking the effect of gene age. While controlling for these factors, we used population genomic data sets of Arabidopsis and Drosophila and estimated the rate of adaptive substitutions across genes from different phylostrata. We found that a gene’s evolutionary age significantly impacts the molecular rate of adaptation. Moreover, we observed that substitutions in young genes tend to have larger physicochemical effects. Our study, therefore, provides strong evidence that molecular evolution follows an adaptive walk model across a large evolutionary timescale

On variant discovery in genomes of fungal plant pathogens

Comparative genome analyses of eukaryotic pathogens including fungi and oomycetes have revealed extensive variability in genome composition and structure. The genomes of individuals from the same population can exhibit different numbers of chromosomes and different organization of chromosomal segments, defining so-called accessory compartments that have been shown to be crucial to pathogenicity in plant-infecting fungi. This high level of structural variation confers a methodological challenge for population genomic analyses. Variant discovery from population sequencing data is typically achieved using established pipelines based on the mapping of short reads to a reference genome. These pipelines have been developed, and extensively used, for eukaryote genomes of both plants and animals, to retrieve single nucleotide polymorphisms and short insertions and deletions. However, they do not permit the inference of large-scale genomic structural variation, as this task typically requires the alignment of complete genome sequences. Here, we compare traditional variant discovery approaches to a pipeline based on de novo genome assembly of short read data followed by whole genome alignment, using simulated data sets with properties mimicking that of fungal pathogen genomes. We show that the latter approach exhibits levels of performance comparable to that of read-mapping based methodologies, when used on sequence data with sufficient coverage. We argue that this approach further allows additional types of genomic diversity to be explored, in particular as long-read third-generation sequencing technologies are becoming increasingly available to generate population genomic data

Plant pathogens provide clues to the potential origin of bat white-nose syndromePseudogymnoascus destructans

White-nose syndrome has killed millions of bats, yet both the origins and infection strategy of the causative fungus, Pseudogymnoascus destructans, remain elusive. We provide evidence for a novel hypothesis that P. destructans emerged from plant-associated fungi and retained invasion strategies affiliated with fungal pathogens of plants. We demonstrate that P. destructans invades bat skin in successive biotrophic and necrotrophic stages (hemibiotrophic infection), a mechanism previously only described in plant fungal pathogens. Further, the convergence of hyphae at hair follicles suggests nutrient tropism. Tropism, biotrophy, and necrotrophy are often associated with structures termed appressoria in plant fungal pathogens; the penetrating hyphae produced by P. destructans resemble appressoria. Finally, we conducted a phylogenomic analysis of a taxonomically diverse collection of fungi. Despite gaps in genetic sampling of prehistoric and contemporary fungal species, we estimate an 88% probability the ancestral state of the clade containing P. destructans was a plant-associated fungus

Dual mobility hip arthroplasty wear measurement: Experimental accuracy assessment using radiostereometric analysis (RSA)

SummaryIntroductionThe use of dual mobility cups is an effective method to prevent dislocations. However, the specific design of these implants can raise the suspicion of increased wear and subsequent periprosthetic osteolysis.HypothesisUsing radiostereometric analysis (RSA), migration of the femoral head inside the cup of a dual mobility implant can be defined to apprehend polyethylene wear rate.Study objectivesThe study aimed to establish the precision of RSA measurement of femoral head migration in the cup of a dual mobility implant, and its intra- and interobserver variability.Material and methodsA total hip prosthesis phantom was implanted and placed under weight loading conditions in a simulator. Model-based RSA measurement of implant penetration involved specially machined polyethylene liners with increasing concentric wear (no wear, then 0.25, 0.5 and 0.75mm). Three examiners, blinded to the level of wear, analyzed (10 times) the radiostereometric films of the four liners. There was one experienced, one trained, and one inexperienced examiner. Statistical analysis measured the accuracy, precision, and intra- and interobserver variability by calculating Root Mean Square Error (RMSE), Concordance Correlation Coefficient (CCC), Intra Class correlation Coefficient (ICC), and Bland-Altman plots.ResultsOur protocol, that used a simple geometric model rather than the manufacturer's CAD files, showed precision of 0.072mm and accuracy of 0.034mm, comparable with machining tolerances with low variability. Correlation between wear measurement and true value was excellent with a CCC of 0.9772. Intraobserver reproducibility was very good with an ICC of 0.9856, 0.9883 and 0.9842, respectively for examiners 1, 2 and 3. Interobserver reproducibility was excellent with a CCC of 0.9818 between examiners 2 and 1, and 0.9713 between examiners 3 and 1.DiscussionQuantification of wear is indispensable for the surveillance of dual mobility implants. This in vitro study validates our measurement method. Our results, and comparison with other studies using different measurement technologies (RSA, standard radiographs, Martell method) make model-based RSA the reference method for measuring the wear of total hip prostheses in vivo.Level of evidenceLevel 3. Prospective diagnostic study

Branch Module for an Inductive Voltage Adder for Driving Kicker Magnets with a Short Circuit Termination

For driving kicker magnets terminated in a short circuit, a branch module for an inductive voltage adder has been designed and assembled. The module has been designed for a maximum charging voltage of 1.2 kV and an output current of 200 A considering the current doubling due to the short circuit termination. It features three consecutive modes of operation: energy injection, freewheeling, and energy extraction. Therefore, the topology of the branch module consists of two independently controlled SiC MOSFET switches and one diode switch. In order not to extend the field rise time of the kicker magnet significantly beyond the magnet fill time, the pulse must have a fast rise time. Hence, the switch for energy injection is driven by a gate boosting driver featuring a half bridge of GaN HEMTs and a driving voltage of 80 V. Measurements of the drain source voltage of this switch showed a fall time of 2.7 ns at a voltage of 600 V resulting in a voltage rise time of 5.4 ns at the output terminated with a resistive load. To meet both the rise time and current requirements, a parallel configuration of four SiC MOSFETs was implemented

Dinosaur footprints and other Ichnofauna from the Cretaceous Kem Kem Beds of Morocco

We describe an extensive ichnofossil assemblage from the likely Cenomanian-age 'lower' and 'upper' units of the 'Kem Kem beds' in southeastern Morocco. In the lower unit, trace fossils include narrow vertical burrows in cross-bedded sandstones and borings in dinosaur bone, with the latter identified as the insect ichnotaxon Cubiculum ornatus. In the upper unit, several horizons preserve abundant footprints from theropod dinosaurs. Sauropod and ornithischian footprints are much rarer, similar to the record for fossil bone and teeth in the Kem Kem assemblage. The upper unit also preserves a variety of invertebrate traces including Conichnus (the resting trace of a sea-anemone), Scolicia (a gastropod trace), Beaconites (a probable annelid burrow), and subvertical burrows likely created by crabs for residence and detrital feeding on a tidal flat. The ichnofossil assemblage from the Upper Cretaceous Kem Kem beds contributes evidence for a transition from predominantly terrestrial to marine deposition. Body fossil and ichnofossil records together provide a detailed view of faunal diversity and local conditions within a fluvial and deltaic depositional setting on the northwestern coast of Africa toward the end of the Cretaceous

Fast and Robust Characterization of Time-Heterogeneous Sequence Evolutionary Processes Using Substitution Mapping

Genes and genomes do not evolve similarly in all branches of the tree of life. Detecting and characterizing the heterogeneity in time, and between lineages, of the nucleotide (or amino acid) substitution process is an important goal of current molecular evolutionary research. This task is typically achieved through the use of non-homogeneous models of sequence evolution, which being highly parametrized and computationally-demanding are not appropriate for large-scale analyses. Here we investigate an alternative methodological option based on probabilistic substitution mapping. The idea is to first reconstruct the substitutional history of each site of an alignment under a homogeneous model of sequence evolution, then to characterize variations in the substitution process across lineages based on substitution counts. Using simulated and published datasets, we demonstrate that probabilistic substitution mapping is robust in that it typically provides accurate reconstruction of sequence ancestry even when the true process is heterogeneous, but a homogeneous model is adopted. Consequently, we show that the new approach is essentially as efficient as and extremely faster than (up to 25 000 times) existing methods, thus paving the way for a systematic survey of substitution process heterogeneity across genes and lineages