Bridging the divide bacteria synthesizing archaeal membrane lipids, bioRxiv, 2018-10-19

Archaea synthesize membranes of isoprenoid lipids that are ether-linked to glycerol, while BacteriaEukarya produce membranes consisting of ester-bound fatty acids. This dichotomy in membrane lipid composition or ‘lipid divide’ is believed to have arisen after the Last Universal Common Ancestor (LUCA). A leading hypothesis is that LUCA possessed a ‘mixed heterochiral archaealbacterial membrane’, however no natural microbial representatives supporting this scenario have been shown to exist today. Here, we demonstrate that bacteria of the Fibrobacteres-Chlorobi-Bacteroidetes (FCB) group superphylum and related candidate phyla encode a complete pathway for archaeal membrane lipid biosynthesis in addition to the bacterial fatty acid membrane pathway. Key genes were expressed in the environment and their recombinant expression in E. coli resulted in the formation of a ‘mixed archaealbacterial membrane’. Our results support the existence of ‘mixed membranes’ in natural environments and their stability over large evolutionary timescales, thereby bridging a once-thought fundamental divide in biology.

Explaining heritable variance in human character, bioRxiv, 2018-10-19

RAxML-NG A fast, scalable, and user-friendly tool for maximum likelihood phylogenetic inference, bioRxiv, 2018-10-19

AbstractMotivationPhylogenies are important for fundamental biological research, but also have numerous applications in biotechnology, agriculture, and medicine. Finding the optimal tree under the popular maximum like-lihood (ML) criterion is known to be NP-hard. Thus, highly optimized and scalable codes are needed to analyze constantly growing empirical datasets.ResultsWe present RAxML-NG, a from scratch re-implementation of the established greedy tree search algorithm of RAxMLExaML. RAxML- NG offers improved accuracy, flexibility, speed, scalability, and usability compared to RAxMLExaML. On taxon-rich datasets, RAxML-NG typically finds higher-scoring trees than IQTree, an increasingly popular recent tool for ML-based phylogenetic inference (although IQ-Tree shows better stability). Finally, RAxML-NG introduces several new features, such as the detection of terraces in tree space and a the recently introduced transfer bootstrap support metric.AvailabilityThe code is available under GNU GPL at <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpsgithub.comamkozlovraxml-ng.RAxML-NG>httpsgithub.comamkozlovraxml-ng.RAxML-NG<jatsext-link> web service (maintained by Vital- IT) is available at <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpsraxml-ng.vital-it.ch>httpsraxml-ng.vital-it.ch<jatsext-link>.Contactalexey.kozlov@h-its.org

Transposon accumulation lines uncover histone H2A.Z-driven integration bias towards environmentally responsive genes, bioRxiv, 2018-10-19

Inherited transposition events are important drivers of genome evolution but because transposable element (TE) mobilization is usually rare, its impact on the creation of genetic variation remains poorly characterized. Here, we used a population of A. thaliana epigenetic recombinant inbred lines (epiRILs) to characterize &gt;8000 de novo insertions produced by several TEs families also active in nature. Integration was strongly biased towards genes, with evident deleterious effects. Biases were TE family-specific and associated with distinct chromatin features. Notably, we demonstrate that the histone variant H2A.Z guides the preferential integration of Ty1Copia LTR-retrotransposons within environmentally responsive genes and that this guiding function is evolutionary conserved. Finally, we uncover an important role for epigenetic silencing in exacerbating or alleviating the effects of TE insertions on target genes. These findings establish chromatin as a major determinant of the spectrum and functional impact of TE-generated mutations, with important implications for adaptation and evolution.

Unraveling the polygenic architecture of complex traits using blood eQTL meta-analysis, bioRxiv, 2018-10-19

While many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear. To identify these effects, we performed cis- and trans-expression quantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium. We observed that cis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting our ability to use cis-eQTLs to pinpoint causal genes within susceptibility loci. In contrast, trans-eQTLs (detected for 37% of 10,317 studied trait-associated variants) were more informative. Multiple unlinked variants, associated to the same complex trait, often converged on trans-genes that are known to play central roles in disease etiology. We observed the same when ascertaining the effect of polygenic scores calculated for 1,263 genome-wide association study (GWAS) traits. Expression levels of 13% of the studied genes correlated with polygenic scores, and many resulting genes are known to drive these traits.

Unraveling the polygenic architecture of complex traits using blood eQTL metaanalysis, bioRxiv, 2018-10-19

SummaryWhile many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear.To identify these effects, we performed cis- and trans-expression quantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium.We observed that cis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting our ability to use cis-eQTLs to pinpoint causal genes within susceptibility loci.In contrast, trans-eQTLs (detected for 37% of 10,317 studied trait-associated variants) were more informative. Multiple unlinked variants, associated to the same complex trait, often converged on trans-genes that are known to play central roles in disease etiology.We observed the same when ascertaining the effect of polygenic scores calculated for 1,263 genome-wide association study (GWAS) traits. Expression levels of 13% of the studied genes correlated with polygenic scores, and many resulting genes are known to drive these traits.