RNA viruses drove adaptive introgressions between Neanderthals and modern humans, bioRxiv, 2017-03-25
AbstractNeanderthals and modern humans came in contact with each other and interbred at least twice in the past 100,000 years. Such contact and interbreeding likely led both to the transmission of viruses novel to either species and to the exchange of adaptive alleles that provided resistance against the same viruses. Here, we show that viruses were responsible for dozens of adaptive introgressions between Neanderthals and modern humans. We identify RNA viruses—specifically lentiviruses and orthomyxoviruses—as likely drivers of introgressions from Neanderthals to Europeans. Our results imply that many introgressions between Neanderthals and modern humans were adaptive, and that host genetic variation can be used to understand ancient viral epidemics, potentially providing important insights regarding current and future epidemics.One Sentence SummaryOnce out of Africa, modern humans inherited from Neanderthals dozens of genes already adapted against viruses present in their new environment.
biorxiv evolutionary-biology 100-200-users 2017Chromatin-associated RNA sequencing (ChAR-seq) maps genome-wide RNA-to-DNA contacts, bioRxiv, 2017-03-21
AbstractRNA is a critical component of chromatin in eukaryotes, both as a product of transcription, and as an essential constituent of ribonucleoprotein complexes that regulate both local and global chromatin states. Here we present a proximity ligation and sequencing method called Chromatin-Associated RNA sequencing (ChAR-seq) that maps all RNA-to-DNA contacts across the genome. ChAR-seq provides unbiased, de novo identification of targets of chromatin-bound RNAs including nascent transcripts, chromosome-specific dosage compensation ncRNAs, and genome-wide trans-associated RNAs involved in co-transcriptional RNA processing.
biorxiv genomics 100-200-users 2017MTAG Multi-Trait Analysis of GWAS, bioRxiv, 2017-03-21
ABSTRACTWe introduce Multi-Trait Analysis of GWAS (MTAG), a method for joint analysis of summary statistics from GWASs of different traits, possibly from overlapping samples. We apply MTAG to summary statistics for depressive symptoms (Neff = 354,862), neuroticism (N = 168,105), and subjective well-being (N = 388,538). Compared to 32, 9, and 13 genome-wide significant loci in the single-trait GWASs (most of which are themselves novel), MTAG increases the number of loci to 64, 37, and 49, respectively. Moreover, association statistics from MTAG yield more informative bioinformatics analyses and increase variance explained by polygenic scores by approximately 25%, matching theoretical expectations.
biorxiv genomics 100-200-users 2017Preservation of Chromatin Organization after Acute Loss of CTCF in Mouse Embryonic Stem Cells, bioRxiv, 2017-03-21
SummaryThe CCCTC-binding factor (CTCF) is widely regarded as a key player in chromosome organization in mammalian cells, yet direct assessment of the impact of loss of CTCF on genome architecture has been difficult due to its essential role in cell proliferation and early embryogenesis. Here, using auxin-inducible degron techniques to acutely deplete CTCF in mouse embryonic stem cells, we show that cell growth is severely slowed yet chromatin organization remains largely intact after loss of CTCF. Depletion of CTCF reduces interactions between chromatin loop anchors, diminishes occupancy of cohesin complex genome-wide, and slightly weakens topologically associating domain (TAD) structure, but the active and inactive chromatin compartments are maintained and the vast majority of TAD boundaries persist. Furthermore, transcriptional regulation and histone marks associated with enhancers are broadly unchanged upon CTCF depletion. Our results suggest CTCF-independent mechanisms in maintenance of chromatin organization.
biorxiv genomics 100-200-users 2017The Drosophila Embryo at Single Cell Transcriptome Resolution, bioRxiv, 2017-03-18
ABSTRACTDrosophila is a premier model system for understanding the molecular mechanisms of development. By the onset of morphogenesis, ~6000 cells express distinct gene combinations according to embryonic position. Despite extensive mRNA in situ screens, combinatorial gene expression within individual cells is largely unknown. Therefore, it is difficult to comprehensively identify the coding and non-coding transcripts that drive patterning and to decipher the molecular basis of cellular identity. Here, we single-cell sequence precisely staged embryos, measuring >3100 genes per cell. We produce a ‘transcriptomic blueprint’ of development – a virtual embryo where 3D locations of sequenced cells are confidently identified. Our “Drosophila-Virtual-Expression-eXplorer” performs virtual in situ hybridizations and computes expression gradients. Using DVEX, we predict spatial expression and discover patterned lncRNAs. DEVX is sensitive enough to detect subtle evolutionary changes in expression patterns between Drosophila species. We believe DVEX is a prototype for powerful single cell studies in complex tissues.
biorxiv genomics 100-200-users 2017Nanotube-mediated cross-feeding couples the metabolism of interacting bacterial cells, bioRxiv, 2017-03-07
ABSTRACTBacteria frequently engage in cross-feeding interactions that involve an exchange of metabolites with other micro- or macroorganisms. The often obligate nature of these associations, however, hampers manipulative experiments, thus limiting our mechanistic understanding of the ecophysiological consequences that result for the organisms involved. Here we address this issue by taking advantage of a well-characterised experimental model system, in which auxotrophic genotypes of E. coli derive essential amino acid from prototrophic donor cells using intercellular nanotubes. Surprisingly, donor-recipient cocultures revealed that the mere presence of auxotrophic genotypes in coculture was sufficient to increase amino acid production levels in donor cells. Subsequent experiments unravelled that this effect was due to the depletion of amino acid concentrations in the cytoplasm of donor cells, which delayed feedback inhibition of the corresponding amino acid biosynthetic pathway. This finding indicates that in newly established mutualistic associations, an intercellular regulation of exchanged metabolites can simply emerge from the architecture of the underlying biosynthetic pathways, rather than through the evolution of new regulatory mechanisms. Taken together, our results show that a single loss-of-function mutation can physiologically couple the metabolism of two cross-feeding cells in a source-sink-like relationship.
biorxiv microbiology 100-200-users 2017