A closed Candidatus Odinarchaeum chromosome exposes Asgard archaeal viruses

Asgard archaea have recently been identified as the closest archaeal relatives of eukaryotes. Their ecology, and particularly their virome, remain enigmatic. We reassembled and closed the chromosome of Candidatus Odinarchaeum yellowstonii LCB_4, through long-range PCR, revealing CRISPR spacers targeting viral contigs. We found related viruses in the genomes of diverse prokaryotes from geothermal environments, including other Asgard archaea. These viruses open research avenues into the ecology and evolution of Asgard archaea

Functional reconstruction of a eukaryotic-like E1/E2/(RING) E3 ubiquitylation cascade from an uncultured archaeon.

The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions. Although it has been established that ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is less clear how complex eukaryotic ubiquitylation system arose and diversified from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like and small-RING finger (srfp) protein components in the Aigarchaeota and the Asgard archaea superphyla has provided a substantive step toward addressing this evolutionary question. Encoded in operons, these components are likely representative of the progenitor apparatus that founded the modern eukaryotic ubiquitin modification systems. Here we report that these proteins from the archaeon Candidatus 'Caldiarchaeum subterraneum' operate together as a bona fide ubiquitin modification system, mediating a sequential ubiquitylation cascade reminiscent of the eukaryotic process. Our observations support the hypothesis that complex eukaryotic ubiquitylation signalling pathways have developed from compact systems originally inherited from an archaeal ancestor

Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes

In the ongoing debates about eukaryogenesis—the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors— members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes1. However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved2–4. Here we analyse distinct phylogenetic marker datasets of an expanded genomic sampling of Asgard archaea and evaluate competing evolutionary scenarios using state-of-the-art phylogenomic approaches. We find that eukaryotes are placed, with high confidence, as a well-nested clade within Asgard archaea and as a sister lineage to Hodarchaeales, a newly proposed order within Heimdallarchaeia. Using sophisticated gene tree and species tree reconciliation approaches, we show that analogous to the evolution of eukaryotic genomes, genome evolution in Asgard archaea involved significantly more gene duplication and fewer gene loss events compared with other archaea. Finally, we infer that the last common ancestor of Asgard archaea was probably a thermophilic chemolithotroph and that the lineage from which eukaryotes evolved adapted to mesophilic conditions and acquired the genetic potential to support a heterotrophic lifestyle. Our work provides key insights into the prokaryote-to-eukaryote transition and a platform for better understanding the emergence of cellular complexity in eukaryotic cells

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

Peer reviewe

Genomic and evolutionary exploration of Asgard archaea

Current evolutionary theories postulate that eukaryotes emerged from the symbiosis of an archaeal host with, at least, one bacterial symbiont. However, our limited grasp of microbial diversity hampers insights into the features of the prokaryotic ancestors of eukaryotes. This thesis focuses on the study of a group of uncultured archaea to better understand both existing archaeal diversity and the origin of eukaryotes. In a first study, we used short-read metagenomic approaches to obtain eight genomes of Lokiarchaeum relatives. Using these data we described the Asgard superphylum, comprised of at least four different phyla: Lokiarchaeota, Odinarchaeota, Thorarchaeota and Heimdallarchaoeta. Phylogenetic analyses suggested that eukaryotes affiliate with the Asgard group, albeit the exact position of eukaryotes with respect to Asgard archaea members remained inconclusive. Comparative genomics showed that Asgard archaea genomes encoded homologs of numerous eukaryotic signature proteins (ESPs), which had never been observed in Archaea before. Among these, there were several components of proteins involved in vesicle formation and membrane remodelling. In a second study, we used similar approaches to uncover additional members of the Asgard superphylum. Based on genome-centric metagenomics we recovered 69 new genomes from which we identified five additional candidate phyla: Freyarchaeota, Baldrarchaeota, Gefionarchaeota, Friggarchaeota and Idunnarchaeota. In this expanded dataset we could detect additional homologs for unreported ESPs. Updated phylogenies showed support for a scenario in which eukaryotes emerged from within Asgard archaea. We further took advantage of the increased Asgard diversity to delimit the gene content of the last common archaeal ancestor of eukaryotes using ancestral reconstruction analyses. The results suggest that the archaeal host cell who gave rise to eukaryotes already contained many of the genes associated with eukaryotic cellular complexity. Based on these analyses, we discussed the metabolic capabilities of the archaeal ancestor of eukaryotes. Finally, we reconstructed several nearly complete Lokiarchaeota genomes, one of them in only three contigs, using both short- and long-read metagenomics. These analyses indicate that long-read metagenomics is a promising approach to obtain highly complete and contiguous genomes directly from environmental samples, even from complex populations in the presence of microdiversity and low abundant members. This study further supports that the presence of ESPs in Asgard genomes is not the result of assembly and binning artefacts.  In conclusion, this thesis highlights the value of using culture-independent approaches together with phylogenomics and comparative genomics to improve our understanding of microbial diversity and to shed light into relevant evolutionary questions

Genomic and evolutionary exploration of Asgard archaea

Current evolutionary theories postulate that eukaryotes emerged from the symbiosis of an archaeal host with, at least, one bacterial symbiont. However, our limited grasp of microbial diversity hampers insights into the features of the prokaryotic ancestors of eukaryotes. This thesis focuses on the study of a group of uncultured archaea to better understand both existing archaeal diversity and the origin of eukaryotes. In a first study, we used short-read metagenomic approaches to obtain eight genomes of Lokiarchaeum relatives. Using these data we described the Asgard superphylum, comprised of at least four different phyla: Lokiarchaeota, Odinarchaeota, Thorarchaeota and Heimdallarchaoeta. Phylogenetic analyses suggested that eukaryotes affiliate with the Asgard group, albeit the exact position of eukaryotes with respect to Asgard archaea members remained inconclusive. Comparative genomics showed that Asgard archaea genomes encoded homologs of numerous eukaryotic signature proteins (ESPs), which had never been observed in Archaea before. Among these, there were several components of proteins involved in vesicle formation and membrane remodelling. In a second study, we used similar approaches to uncover additional members of the Asgard superphylum. Based on genome-centric metagenomics we recovered 69 new genomes from which we identified five additional candidate phyla: Freyarchaeota, Baldrarchaeota, Gefionarchaeota, Friggarchaeota and Idunnarchaeota. In this expanded dataset we could detect additional homologs for unreported ESPs. Updated phylogenies showed support for a scenario in which eukaryotes emerged from within Asgard archaea. We further took advantage of the increased Asgard diversity to delimit the gene content of the last common archaeal ancestor of eukaryotes using ancestral reconstruction analyses. The results suggest that the archaeal host cell who gave rise to eukaryotes already contained many of the genes associated with eukaryotic cellular complexity. Based on these analyses, we discussed the metabolic capabilities of the archaeal ancestor of eukaryotes. Finally, we reconstructed several nearly complete Lokiarchaeota genomes, one of them in only three contigs, using both short- and long-read metagenomics. These analyses indicate that long-read metagenomics is a promising approach to obtain highly complete and contiguous genomes directly from environmental samples, even from complex populations in the presence of microdiversity and low abundant members. This study further supports that the presence of ESPs in Asgard genomes is not the result of assembly and binning artefacts.  In conclusion, this thesis highlights the value of using culture-independent approaches together with phylogenomics and comparative genomics to improve our understanding of microbial diversity and to shed light into relevant evolutionary questions

Genomic exploration of the diversity, ecology, and evolution of the archaeal domain of life

About 40 years ago, Archaea were recognized as a major prokaryotic domain of life besides Bacteria. Recently, cultivation-independent sequencing methods have produced a wealth of genomic data for previously unidentified archaeal lineages, several of which appear to represent newly revealed branches in the tree of life. Analyses of some recently obtained genomes have uncovered previously unknown metabolic traits and provided insights into the evolution of archaea and their relationship to eukaryotes. On the basis of our current understanding, much archaeal diversity still defies genomic exploration. Efforts to obtain and study genomes and enrichment cultures of uncultivated microbial lineages will likely further expand our knowledge about archaeal phylogenetic and metabolic diversity and their cell biology and ecological function.</p

Complex Evolutionary History of Translation Elongation Factor 2 and Diphthamide Biosynthesis in Archaea and Parabasalids

Diphthamide is a modified histidine residue which is uniquely present in archaeal and eukaryotic elongation factor 2 (EF-2), an essential GTPase responsible for catalyzing the coordinated translocation of tRNA and mRNA through the ribosome. In part due to the role of diphthamide in maintaining translational fidelity, it was previously assumed that diphthamide biosynthesis genes (dph) are conserved across all eukaryotes and archaea. Here, comparative analysis of new and existing genomes reveals that some archaea (i.e., members of the Asgard superphylum, Geoarchaea, and Korarchaeota) and eukaryotes (i.e., parabasalids) lack dph. In addition, while EF-2 was thought to exist as a single copy in archaea, many of these dph-lacking archaeal genomes encode a second EF-2 paralog missing key residues required for diphthamide modification and for normal translocase function, perhaps suggesting functional divergence linked to loss of diphthamide biosynthesis. Interestingly, some Heimdallarchaeota previously suggested to be most closely related to the eukaryotic ancestor maintain dph genes and a single gene encoding canonical EF-2. Our findings reveal that the ability to produce diphthamide, once thought to be a universal feature in archaea and eukaryotes, has been lost multiple times during evolution, and suggest that anticipated compensatory mechanisms evolved independently