Phylogenomics of Unusual Histone H2A Variants in Bdelloid Rotifers

Rotifers of Class Bdelloidea are remarkable in having evolved for millions of years, apparently without males and meiosis. In addition, they are unusually resistant to desiccation and ionizing radiation and are able to repair hundreds of radiation-induced DNA double-strand breaks per genome with little effect on viability or reproduction. Because specific histone H2A variants are involved in DSB repair and certain meiotic processes in other eukaryotes, we investigated the histone H2A genes and proteins of two bdelloid species. Genomic libraries were built and probed to identify histone H2A genes in Adineta vaga and Philodina roseola, species representing two different bdelloid families. The expressed H2A proteins were visualized on SDS-PAGE gels and identified by tandem mass spectrometry. We find that neither the core histone H2A, present in nearly all other eukaryotes, nor the H2AX variant, a ubiquitous component of the eukaryotic DSB repair machinery, are present in bdelloid rotifers. Instead, they are replaced by unusual histone H2A variants of higher mass. In contrast, a species of rotifer belonging to the facultatively sexual, desiccation- and radiation-intolerant sister class of bdelloid rotifers, the monogononts, contains a canonical core histone H2A and appears to lack the bdelloid H2A variant genes. Applying phylogenetic tools, we demonstrate that the bdelloid-specific H2A variants arose as distinct lineages from canonical H2A separate from those leading to the H2AX and H2AZ variants. The replacement of core H2A and H2AX in bdelloid rotifers by previously uncharacterized H2A variants with extended carboxy-terminal tails is further evidence for evolutionary diversity within this class of histone H2A genes and may represent adaptation to unusual features specific to bdelloid rotifers

The repertoire of ICE in prokaryotes underscores the unity, diversity, and ubiquity of conjugation

Horizontal gene transfer shapes the genomes of prokaryotes by allowing rapid acquisition of novel adaptive functions. Conjugation allows the broadest range and the highest gene transfer input per transfer event. While conjugative plasmids have been studied for decades, the number and diversity of integrative conjugative elements (ICE) in prokaryotes remained unknown. We defined a large set of protein profiles of the conjugation machinery to scan over 1,000 genomes of prokaryotes. We found 682 putative conjugative systems among all major phylogenetic clades and showed that ICEs are the most abundant conjugative elements in prokaryotes. Nearly half of the genomes contain a type IV secretion system (T4SS), with larger genomes encoding more conjugative systems. Surprisingly, almost half of the chromosomal T4SS lack co-localized relaxases and, consequently, might be devoted to protein transport instead of conjugation. This class of elements is preponderant among small genomes, is less commonly associated with integrases, and is rarer in plasmids. ICEs and conjugative plasmids in proteobacteria have different preferences for each type of T4SS, but all types exist in both chromosomes and plasmids. Mobilizable elements outnumber self-conjugative elements in both ICEs and plasmids, which suggests an extensive use of T4SS in trans. Our evolutionary analysis indicates that switch of plasmids to and from ICEs were frequent and that extant elements began to differentiate only relatively recently. According to the present results, ICEs are the most abundant conjugative elements in practically all prokaryotic clades and might be far more frequently domesticated into non-conjugative protein transport systems than previously thought. While conjugative plasmids and ICEs have different means of genomic stabilization, their mechanisms of mobility by conjugation show strikingly conserved patterns, arguing for a unitary view of conjugation in shaping the genomes of prokaryotes by horizontal gene transfer

The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences

Neanderthal behaviour, diet, and disease inferred from ancient DNA in dental calculus

Recent genomic data have revealed multiple interactions between Neanderthals and modern humans, but there is currently little genetic evidence regarding Neanderthal behaviour, diet, or disease. Here we describe the shotgun-sequencing of ancient DNA from five specimens of Neanderthal calcified dental plaque (calculus) and the characterization of regional differences in Neanderthal ecology. At Spy cave, Belgium, Neanderthal diet was heavily meat based and included woolly rhinoceros and wild sheep (mouflon), characteristic of a steppe environment. In contrast, no meat was detected in the diet of Neanderthals from El Sidrón cave, Spain, and dietary components of mushrooms, pine nuts, and moss reflected forest gathering. Differences in diet were also linked to an overall shift in the oral bacterial community (microbiota) and suggested that meat consumption contributed to substantial variation within Neanderthal microbiota. Evidence for self-medication was detected in an El Sidrón Neanderthal with a dental abscess and a chronic gastrointestinal pathogen (Enterocytozoon bieneusi). Metagenomic data from this individual also contained a nearly complete genome of the archaeal commensal Methanobrevibacter oralis (10.2× depth of coverage)-the oldest draft microbial genome generated to date, at around 48,000 years old. DNA preserved within dental calculus represents a notable source of information about the behaviour and health of ancient hominin specimens, as well as a unique system that is useful for the study of long-term microbial evolution

Genomic Surveillance of Yellow Fever Virus Epizootic in São Paulo, Brazil, 2016 – 2018

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species

Movement assessment in patients with cerebral motor disorders using accelerometers

This thesis investigates the limitations of the existing solutions for movement assessment in daily clinical practices. The Clinical Cerebral Movement Assessment Tool (CCMAT) is presented as a cost-effective and portable solution for movement assessment in daily clinical practices. The tool has been based on the actual needs of movement disorder specialists for movement assessment. The CCMAT is solely based on accelerometer sensors. It has been validated for two of the main cerebral motor disorders, i.e. stroke and Parkinson's disease (PD). The CCMAT is first validated against the gold standard Codamotion system during a reach and grasp task which is generally used for post-stroke rehabilitation. An error model Kalman filter is used to extract the dynamic accelerations due to the movements from the CCMAT which are then placed in the global Codamotion frame instead of the sensor frames for comparison. Features are extracted from both systems and compared, showing similar performances. The CCMAT is then used to predict finger tapping clinimetric scores in PD in order to improve the diagnosis accuracy of the disease. Clinimetric rating scales such as the Unified Parkinson's Disease Rating Scale (UPDRS) are widely used in the medical community even though they may be subjective. The CCMAT is used to provide clinimetric scores based on movement features used to depict the finger tapping performances. Finally, the CCMAT is used for gait assessment in PD. The system allows to extract spatio-temporal parameters which can help identify gait deviations, perform better diagnosis, determine appropriate therapy, and monitor patient progress. The CCMAT also allows to detect PD specific impairments such as gait asymmetries and freezing of gait.(FSA 3) -- UCL, 201

NEURAL CORRELATES OF GAIT HYPOKINESIA IN PARKINSON'S DISEASE: AN FMRI STUDY

Introduction: Brisk walking (BW) is an efficient tool to study gait hypokinesia whose pathogenesis remains poorly understood in Parkinson's disease (PD). Aims: Assuming that brain regions recruited during imagined gait strongly overlap with those recruited during real gait, we used mental imagery of BW as a paradigm to study the neural correlates of gait hypokinesia in PD with BOLD fMRI. Methods: 15 'on-drugs' PD patients and 15 controls matched for age and gender were instructed to imagine themselves in two situations: comfortable walking (CW) and BW on a 25 meter-path. Imagined speed reserve (ISR), defined as the difference between imagined BW and CW speeds, was measured as a control of behavioral performance. The first-level individual contrast images representing the comparison between BW and CW were entered into second-level analyses with the corresponding ISRs as correlation regressors. Results: ISRs and their real counterparts measured offline were significantly decreased in patients relatively to controls. They strongly positively correlated in patients (Pearson's r = 0.88) and controls (Pearson's r = 0.59). Between-group comparison of individual contrasts BW minus CW in correlation with their corresponding ISRs showed that increasing imagined gait speed was strongly associated with increased activity of the left posterior parietal cortex (PPC) in controls and with decreased activity of this region in the patients. Conclusions: Our findings suggest that gait hypokinesia is related to an impaired function of the left PPC in PD. The left PPC may represent a target for therapeutic interventions aimed at alleviating gait disturbances in PD

Finger Tapping feature extraction in Parkinson's disease using low-cost accelerometers

peer reviewedThe clinical hallmarks of Parkinson's disease (PD) are movement poverty and slowness (i.e. bradykinesia), muscle rigidity and limb tremor. The physicians usually quantify these motor disturbances by assigning a severity score according to validated but time-consuming clinical scales such as the Unified Parkinson's Disease Rating Scale (UPDRS) - part III. These clinical ratings are however prone to subjectivity and inter-rater variability. The PD medical community is therefore looking for a faster and more objective rating method. As a first step towards this goal, a tri-axial accelerometer-based system is proposed as patients are engaged in a repetitive finger tapping task, which is classically used to assess bradykinesia in the UPDRS-III. After developing the hardware, an algorithm has been developed, that automatically epoched the signal on a trial-by-trial basis and quantified, among others, movement speed, amplitude, hesitations or halts as validated by visual inspection of video recordings during the task. The results obtained in a PD patient and an healthy volunteer are presented. Preliminary results show that PD patients and healthy volunteers have different features profiles, so that a classifier could be set up to predict objective UPDRS-III scores