Project description:Stochastic changes in cytosine methylation are a source of heritable epigenetic and phenotypic diversity in plants. Using the model plant Arabidopsis thaliana, we derive robust estimates of the rate at which methylation is spontaneously gained (forward epimutation) or lost (backward epimutation) at individual cytosines and construct a comprehensive picture of the epimutation landscape in this species. We demonstrate that the dynamic interplay between forward and backward epimutations is modulated by genomic context and show that subtle contextual differences have profoundly shaped patterns of methylation diversity in A. thaliana natural populations over evolutionary timescales. Theoretical arguments indicate that the epimutation rates reported here are high enough to rapidly uncouple genetic from epigenetic variation, but low enough for new epialleles to sustain long-term selection responses. Our results provide new insights into methylome evolution and its population-level consequences. MethylC-seq of Arabidopsis thaliana
Project description:Campylobacter jejuni is one of the leading causes of bacterial diarrhea worldwide and the most common antecedent in peripheral neuropathies such as Guillain Barré and Miller Fisher syndromes (Blaser et al., 2000). Despite the medical and socioeconomic importance of C. jejuni, the proportion of human disease caused by different sources of infection remains unclear. Indeed, this issue has hindered effective control strategies against reducing C. jejuni levels from the food chain. Up to date, a vast number of phenotypic and genotypic typing systems and a large number of databases have been developed in order to determine the different Campylobacter infection sources. However, traditional methods are unable to discriminate strains from different sources that are responsible for causing disease in humans. Interestingly, DNA microarrays represent a technological alternative to compare entire genomes, allowing the identification of all the genes present or absent in a particular strain by comparison with the genome of the reference strain present in the microarray. Previous comparative genomic hybridazation studies of C. jejuni using DNA microarrays have focused on the genetic variability in C. jejuni (Dorrell et al., 2001), which suggest that this organism has high levels of genetic diversity and low levels of genetic plasticity (Taboada et al., 2004). On that account, the aim of this study was based on a comparison by CGH (Comparative Genomic Hybridization) using DNA microarrays for determining the degree of genomic variability of C. jejuni strains from different geographical areas and sources of isolation. This system enabled us to identify possible genes that could be used as genetic markers predictive of infection source. Furthermore, CGH data provide additional information that could be useful for the formulation of new hypotheses about C. jejuni genome evolution, virulence, pathogenicity, and host specificity.
Project description:Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed using genetic data alone and encompassing over 100 events occurring over the past 4,000 years. We identify events whose dates and participants suggest they describe genetic impacts of the Mongol Empire, Arab slave trade, Bantu expansion, first millennium CE migrations in eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations. 158 indviduals of Eurasian descent included as part of a global analysis of admixture
Project description:Stochastic changes in cytosine methylation are a source of heritable epigenetic and phenotypic diversity in plants. Using the model plant Arabidopsis thaliana, we derive robust estimates of the rate at which methylation is spontaneously gained (forward epimutation) or lost (backward epimutation) at individual cytosines and construct a comprehensive picture of the epimutation landscape in this species. We demonstrate that the dynamic interplay between forward and backward epimutations is modulated by genomic context and show that subtle contextual differences have profoundly shaped patterns of methylation diversity in A. thaliana natural populations over evolutionary timescales. Theoretical arguments indicate that the epimutation rates reported here are high enough to rapidly uncouple genetic from epigenetic variation, but low enough for new epialleles to sustain long-term selection responses. Our results provide new insights into methylome evolution and its population-level consequences.
Project description:Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed using genetic data alone and encompassing over 100 events occurring over the past 4,000 years. We identify events whose dates and participants suggest they describe genetic impacts of the Mongol Empire, Arab slave trade, Bantu expansion, first millennium CE migrations in eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations.
Project description:For this study, we created three highly representational different sized genomic libraries of P. aeruginosa PAO1 within the vector pBTB-1. Vector pBTB-1 is a low copy number broad host range plasmid containing a Ã-lactamase resistance marker, a pBAD promoter upstream of the cloning site, as well as transcriptional terminators flanking the cloning site to aid in insert stability. These libraries were transformed into the recombination-deficient P. aeruginosa PAO1 mutant, PAO2003, pooled, and parallel selections performed to identify via traditional sequencing or SCALEs the genomic regions capable of conferring increased tolerance to amikacin, gentamicin, or tobramycin. These antibiotics are all structurally related but have differing substitution patterns on their aminoglycoside backbones. These differences in structure and substitution patterns impact the activity of each antibiotic. We chose to study three different aminoglycosides in attempts to identify genomic regions capable of conferring resistance to not only a specific aminoglycoside, but also to the more general class of aminoglycosides.
Project description:Chromatin plays roles in processes governed by different time scales. To assay the dynamic behaviour of chromatin in living cells, we used genomic tiling arrays to measure histone H3 turnover in G1-arrested S. cerevisiae at single-nucleosome resolution over 4% of the genome, and over the entire genome at lower (~265 bp) resolution. We find that nucleosomes at promoters are replaced more rapidly than at coding regions, and that replacement rates over coding regions correlate with polymerase density. In addition, rapid histone turnover is found at known chromatin boundary elements. These results suggest that rapid histone turnover serves to functionally separate chromatin domains and prevent spread of histone states. Keywords: MNase, Nucleosomes Nucleosomal vs genomic DNA.