Response to Pervasive Sequence Patents Cover the Entire Human Genome

In a widely reported article by Jeffrey Rosenfeld and Christopher Mason published in Genome Medicine, significant misstatements were made, because the authors did not sufficiently review the claims – which define the legal scope of a patent – in the patents they analyzed. Specifically, the authors do not provide an adequate basis for their assertion that 41% of the genes in the human genome have been claimed

Intramural child burials in Iron Age Navarra: How ancient DNA can contribute to household archaeology

The transition from the Late Bronze to the Iron Age on the Iberian Peninsula saw a shift in mortuary customs from mainly inhumation to cremation of the deceased. The poor preservation characteristic of cremated skeletal remains has hindered molecular analyses (isotope analyses, ancient DNA) of the Iberian Final Bronze and Iron Age communities of Iberia. Incidentally, a limited number of young children, often newborns, were exempt from the predominant cremation ritual, in favour of intramural inhumations inside buildings at certain settlements. The discourse surrounding the mean- ing and interpretation of this particular burial rite has developed over a long time in Iberian archaeology but has always been hampered by the limited anthropological, archaeological, and molecular data from these intramural inhumations. Here, we study the genomes of 37 intramurally buried children found in three Early Iron Age settlements, dated between c. 800–450 BC. Population genetic analyses on the newly reported individuals extend our understanding of ancient Iberia by revealing previously unsampled genetic diversity as well as showing a lesser influence of Mediterranean ancestry than on previously published Iron Age individuals from northern Spain. We also provide insights into the sex and biological relatedness of the children, and in so doing, elucidate differ- ent aspects of the intramural burial ritual and building use in settlements. More broadly, the genetic data from these individuals fill an important gap in the archaeogenetic record of northern Spain and offer a unique opportunity to study the genetic makeup and population changes from the Bronze Age to Antiquity.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 851511). It has also been supported by the research project »Convergence and interaction between complex Bronze Age societies« from the Academia program of the Institució Catalana de Recerca i Estudis Avançats (ICREA) of the Catalan Government and the Spanish Ministry for Science and Innovation (PID2020-112909GB-100)

The Peptide Antibiotic Corramycin Adopts a β-Hairpin-like Structure and Is Inactivated by the Kinase ComG

The rapid development of antibiotic resistance, especially among difficult-to-treat Gram-negative bacteria, is recognized as a serious and urgent threat to public health. The detection and characterization of novel resistance mechanisms are essential to better predict the spread and evolution of antibiotic resistance. Corramycin is a novel and modified peptidic antibiotic with activity against several Gram-negative pathogens. We demonstrate that the kinase ComG, part of the corramycin biosynthetic gene cluster, phosphorylates and thereby inactivates corramycin, leading to the resistance of the host. Remarkably, we found that the closest structural homologues of ComG are aminoglycoside phosphotransferases; however, ComG shows no activity toward this class of antibiotics. The crystal structure of ComG in complex with corramycin reveals that corramycin adopts a β-hairpin-like structure and allowed us to define the changes leading to a switch in substrate from sugar to peptide. Bioinformatic analyses suggest a limited occurrence of ComG-like proteins, which along with the absence of cross-resistance to clinically used drugs positions corramycin as an attractive antibiotic for further development

Modeling Small Scale Impacts of Multi-Purpose Platforms: An Ecosystem Approach

Aquaculture and marine renewable energy are two expanding sectors of the Blue Economy in Europe. Assessing the long-term environmental impacts in terms of eutrophication and noise is a priority for both the EU Water Framework Directive and the Marine Strategy Framework Directive, and cumulative impacts will be important for the Maritime Spatial Planning under the Integrated Maritime Policy. With the constant expansion of aquaculture production, it is expected that farms might be established further offshore in more remote areas, as high-energy conditions offer an opportunity to generate more power locally using Marine Renewable Energy (MRE) devices. A proposed solution is the co-location of MRE devices and aquaculture systems using Multi-Purpose Platforms (MPPs) comprising offshore wind turbines (OWTs) that will provide energy for farm operations as well as potentially shelter the farm. Disentangling the impacts, conflicts and synergies of MPP elements on the surrounding marine ecosystem is challenging. Here we created a high-resolution spatiotemporal Ecospace model of the West of Scotland, in order to assess impacts of a simple MPP configuration on the surrounding ecosystem and how these impacts can cascade through the food web. The model evaluated the following specific ecosystem responses: (i) top-down control pathways due to distribution changes among top-predators (harbor porpoise, gadoids and seabirds) driven by attraction to the farming sites and/or repulsion/killing due to OWT operations; (ii) bottom-up control pathways due to salmon farm activity providing increasing benthic enrichment predicated by a fish farm particle dispersal model, and sediment nutrient fluxes to the water column by early diagenesis of organic matter (recycled production). Weak responses of the food-web were found for top-down changes, whilst the results showed high sensitivity to increasing changes of bottom-up drivers that cascaded through the food-web from primary producers and detritus to pelagic and benthic consumers, respectively. We assessed the sensitivity of the model to each of these impacts and the cumulative effects on the ecosystem, discuss the capabilities and limitations of the Ecospace modeling approach as a potential tool for marine spatial planning and the impact that these results could have for the Blue Economy and the EU’s New Green Deal

Cases of trisomy 21 and trisomy 18 among historic and prehistoric individuals discovered from ancient DNA

Aneuploidies, and in particular, trisomies represent the most common genetic aberrations observed in human genetics today. To explore the presence of trisomies in historic and prehistoric populations we screen nearly 10,000 ancient human individuals for the presence of three copies of any of the target autosomes. We find clear genetic evidence for six cases of trisomy 21 (Down syndrome) and one case of trisomy 18 (Edwards syndrome), and all cases are present in infant or perinatal burials. We perform comparative osteological examinations of the skeletal remains and find overlapping skeletal markers, many of which are consistent with these syndromes. Interestingly, three cases of trisomy 21, and the case of trisomy 18 were detected in two contemporaneous sites in early Iron Age Spain (800-400 BCE), potentially suggesting a higher frequency of burials of trisomy carriers in those societies. Notably, the care with which the burials were conducted, and the items found with these individuals indicate that ancient societies likely acknowledged these individuals with trisomy 18 and 21 as members of their communities, from the perspective of burial practice

Genomic transformation and social organization during the Copper Age-Bronze Age transition in southern Iberia

The emerging Bronze Age (BA) of southeastern Iberia saw marked social changes. Late Copper Age (CA) settlements were abandoned in favor of hilltop sites, and collective graves were largely replaced by single or double burials with often distinctive grave goods indirectly reflecting a hierarchical social organization, as exemplified by the BA El Argar group. We explored this transition from a genomic viewpoint by tripling the amount of data available for this period. Concomitant with the rise of El Argar starting ∼2200 cal BCE, we observe a complete turnover of Y-chromosome lineages along with the arrival of steppe-related ancestry. This pattern is consistent with a founder effect in male lineages, supported by our finding that males shared more relatives at sites than females. However, simple two-source models do not find support in some El Argar groups, suggesting additional genetic contributions from the Mediterranean that could predate the BA.This work was supported by the Max Planck Society (V.V.-M. and W.H.); European Research Council (ERC) grant 771234—PALEoRIDER (W.H.); Spanish Ministry of Economy, Industry and Competitiveness project HAR2017-85962-P (C.O., C.R.-H., M.I.F., E.C.B., C.V.-F., V.L., R.M., and R.R.); AGAUR 2017SGR1044 (C.O., C.R.-H., M.I.F., E.C.B., C.V.-F., V.L., R.M., and R.R.); ICREA Academia program (R.R.); John Templeton Foundation grant 61220 (D.R.); and Paul Allen Family Foundation (D.R.). D.R. is an Investigator of the Howard Hughes Medical Institute

Genomic transformation and social organization during the Copper Age-Bronze Age transition in southern Iberia

[EN]The emerging Bronze Age (BA) of southeastern Iberia saw marked social changes. Late Copper Age (CA) settlements were abandoned in favor of hilltop sites, and collective graves were largely replaced by single or double burials with often distinctive grave goods indirectly reflecting a hierarchical social organization, as exemplified by the BA El Argar group. We explored this transition from a genomic viewpoint by tripling the amount of data available for this period. Concomitant with the rise of El Argar starting similar to 2200 cal BCE, we observe a complete turnover of Y-chromosome lineages along with the arrival of steppe-related ancestry. This pattern is consistent with a founder effect in male lineages, supported by our finding that males shared more relatives at sites than females. However, simple two-source models do not find support in some El Argar groups, suggesting additional genetic contributions from the Mediterranean that could predate the BA.This work was supported by the Max Planck Society (V.V.-M. and W.H.); European Research Council (ERC) grant 771234-PALEoRIDER (W. H.); Spanish Ministry of Economy, Industry and Competitiveness project HAR2017-85962-P (C.O., C.R.-H., M.I.F., E.C.B., C.V.-F., V.L., R.M., and R.R.); AGAUR 2017SGR1044 (C.O., C.R.-H., M.I.F., E. C.B., C.V.-F., V. L., R.M., and R.R.); ICREA Academia program (R.R.); John Templeton Foundation grant 61220 (D.R.); and Paul Allen Family Foundation (D.R.). D.R. is an Investigator of the Howard Hughes Medical Institute

Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia

We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10-9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD's polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology