Project description:Gene order, or microsynteny, is generally thought not to be conserved across metazoan phyla. Only a handful of exceptions, typically of tandemly duplicated genes such as Hox genes, have been discovered. Here, we performed a systematic survey for microsynteny conservation in 17 genomes and identified nearly 600 pairs of unrelated genes that have remained together across over 600 million years of evolution. Using multiple genome-wide resources, including several genomic features, epigenetic marks, sequence conservation and microarray expression data, we provide extensive evidence that many of these ancient microsyntenic arrangements have been conserved in order to preserve either (i) the coordinated transcription of neighboring genes, or (ii) Genomic Regulatory Blocks (GRBs), in which transcriptional enhancers controlling key developmental genes are contained within nearby “bystander” genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos to further investigate putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results show that ancient genomic associations are far more common in modern metazoans than previously thought – likely involving over 12% of the ancestral bilaterian genome – and that cis-regulatory constraints have played a major role in conserving the architecture of metazoan genomes. ChIP-seq H3K27me3 of 24hpf zebrafish embryos
Project description:<p>Residues from ancient artifacts can help identify which plant species were used for their psychoactive properties, providing important information regarding the deep-time co-evolutionary relationship between plants and humans. However, relying on the presence or absence of one or several biomarkers has limited the ability to confidently connect residues to particular plants. We describe a comprehensive metabolomics-based approach that can distinguish closely related species and provide greater confidence in species use determinations. An approximately 1430-year-old pipe from central Washington State not only contained nicotine, but also had strong evidence for the smoking of <em>Nicotiana quadrivalvis</em> and <em>Rhus glabra</em>, as opposed to several other species in this pre-contact pipe. Analysis of a post-contact pipe suggested use of different plants, including the introduced trade tobacco, <em>Nicotiana rustica</em>. Ancient residue metabolomics provides a new frontier in archaeo-chemistry, with greater precision to investigate the evolution of drug use and similar plant-human co-evolutionary dynamics.</p>
Project description:We investigate how a protein-protein interaction between two ancient transcriptional regulators (a homeodomain and MADS box protein) was gained approximately 200 million years ago in a clade of ascomycete yeasts that includes Saccharomyces cerevisiae. We combine deep mutational scanning of Matα2 with a functional selection for cooperative gene expression and tested millions of possible alternative evolutionary solutions to this interaction interface. Pooled Matα2 mutants were deeply sequenced before and after selection for functional Matα2-Mcm1 interaction. The changes in frequency of each variant allowed us to determine their relative fitness.
Project description:Gene order, or microsynteny, is generally thought not to be conserved across metazoan phyla. Only a handful of exceptions, typically of tandemly duplicated genes such as Hox genes, have been discovered. Here, we performed a systematic survey for microsynteny conservation in 17 genomes and identified nearly 600 pairs of unrelated genes that have remained together across over 600 million years of evolution. Using multiple genome-wide resources, including several genomic features, epigenetic marks, sequence conservation and microarray expression data, we provide extensive evidence that many of these ancient microsyntenic arrangements have been conserved in order to preserve either (i) the coordinated transcription of neighboring genes, or (ii) Genomic Regulatory Blocks (GRBs), in which transcriptional enhancers controlling key developmental genes are contained within nearby “bystander” genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos to further investigate putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results show that ancient genomic associations are far more common in modern metazoans than previously thought – likely involving over 12% of the ancestral bilaterian genome – and that cis-regulatory constraints have played a major role in conserving the architecture of metazoan genomes.
Project description:The Caucasus, inhabited by modern humans since the Early Upper Paleolithic and known for its linguistic diversity, is considered to be important for understanding human dispersals and genetic diversity in Eurasia. We report a synthesis of autosomal, Y chromosome, and mitochondrial DNA (mtDNA) variation in populations from all major subregions and linguistic phyla of the area. Autosomal genome variation in the Caucasus reveals significant genetic uniformity among its ethnically and linguistically diverse populations and is consistent with predominantly Near/Middle Eastern origin of the Caucasians, with minor external impacts. In contrast to autosomal and mtDNA variation, signals of regional Y chromosome founder effects distinguish the eastern from western North Caucasians. Genetic discontinuity between the North Caucasus and the East European Plain contrasts with continuity through Anatolia and the Balkans, suggesting major routes of ancient gene flows and admixture. 204 samples were analysed with the Illumina platform Human610-Quad v 1.0 and are described herein.
Project description:Detailed investigation of extremely severe pathological conditions present in ancient human skeletons is important because they can illuminate the breadth of potential interactions between humans and disease etiologies in the past. Here, we applied palaeoproteomics to investigate the bacterial pathogenic factors and host defense response to an ancient human skeletal individual with severe oral pathology. This female skeleton, from the Okhotsk period (i.e., 5th–13th century) of northern Japan, poses abnormal deposition of large amounts of dental calculus and oral dysfunction due to severe periodontal disease. A shotgun mass-spectrometry analysis identified 81 human proteins and 15 bacterial proteins from her calculus. Two pathogenic or bio-invasive proteins originating from two of the three “red complex” bacteria, the core species associated with severe periodontal disease in modern humans, as well as additional two bio-invasive proteins of periodont-associated bacteria were identified. Human proteins associated with the defense response system were identified, but their proportion was mostly similar to that reported in ancient and modern human individuals with lower calculus deposition. These results suggest that the bacterial etiology was similar and the host defense response was not necessarily higher in ancient individuals with abnormal deposition of large amounts of dental calculus.