Evolutionary implications of inversions that have caused intra-strand parity in DNA

BACKGROUND: Chargaff's rule of DNA base composition, stating that DNA comprises equal amounts of adenine and thymine (%A = %T) and of guanine and cytosine (%C = %G), is well known because it was fundamental to the conception of the Watson-Crick model of DNA structure. His second parity rule stating that the base proportions of double-stranded DNA are also reflected in single-stranded DNA (%A = %T, %C = %G) is more obscure, likely because its biological basis and significance are still unresolved. Within each strand, the symmetry of single nucleotide composition extends even further, being demonstrated in the balance of di-, tri-, and multi-nucleotides with their respective complementary oligonucleotides. RESULTS: Here, we propose that inversions are sufficient to account for the symmetry within each single-stranded DNA. Human mitochondrial DNA does not demonstrate such intra-strand parity, and we consider how its different functional drivers may relate to our theory. This concept is supported by the recent observation that inversions occur frequently. CONCLUSION: Along with chromosomal duplications, inversions must have been shaping the architecture of genomes since the origin of life

Characterization of the differentially methylated region of the Impact gene that exhibits Glires-specific imprinting

Comparative genomic analysis of the Impact locus, which is imprinted in Glires but not in other mammals, reveals features required for genomic imprinting

Changepoint detection in base-resolution methylome data reveals a robust signature of methylated domain landscape

ABSTRACTLotta Dalenius Hahlin (2010) Mentorskap utifrån ett lösningsinriktat fokus. (Mentorship based on a solution-oriented focus. Skolutveckling och ledarskap, Lärarutbildningen halvfart/distans, Malmö HögskolaMånga elever hoppar av sin gymnasieutbildning pga. av olika orsaker. En av orsakerna kan vara att eleven inte har tillräckligt stöd i sin mentor på skolan. En mentor skall ju inte bara ta hand om elevens studiemässiga resultat utan får även ta hand om de många sociala frågor som ofta uppstår runt eleven. Kan det vara så att mentorn behöver en ram och metod att arbeta utifrån för att kunna stödja eleverna på bästa sätt?Syftet med arbetet är att beskriva den metodik som ligger bakom ett lösningsinriktat mentorskap,och att skapa ett kompendium av användbara verktyg utifrån lösningsinriktad pedagogik. Detta kompendium kan mentorn använda som mall/ram i sin arbetsuppgift som mentor.Forskningen tyder på att lyckade och bra samtal bygger på bra förberedelse, på öppna frågor och på ömsesidig respekt för varandra och att man använder sig av ett visst förhållningssätt gentemot varandra. Vidare pekar litteraturstudien på att mentorssamtalet bör ha tydliga mål och en gemensam uppfattning om vad man vill komma fram till för att eleven skall nå ökat ansvar, större självinsikt och önskat läge.Arbetet tar upp de olika verktyg som man främst använder inom lösningsinriktade metoder, och är utifrån litteraturen kommenterat för att ge en grundläggande kunskap och förförståelse för läsaren.Genom att som resultat skapa ett kompendium som mentorer kan använda i sitt arbete med det dagliga samtalet med eleverna, vill uppsatsen beskriva och ge grundläggande kunskap om de verktyg som finns i den lösningsinriktade verktygslådan. Syftet nås även med en enkätundersökning där mentorer som fått pröva på metoden plockat ut fördelar och nackdelar med metoden.Uppsatsen visar att regelbunden användning och övning krävs för att kunna tillgodogöra sig metoden, och även att mentorn genomgår en grundläggande utbildning. Den kommer också att visa att vinsterna och fördelarna med metoden överstiger de eventuella nackdelar som kan uppstå när man som mentor börjar arbeta med metoden

Whole-exome sequencing of fibroblast and its iPS cell lines derived from a patient diagnosed with xeroderma pigmentosum

AbstractCells from a patient with a DNA repair-deficiency disorder are anticipated to bear a large number of somatic mutations. Because such mutations occur independently in each cell, there is a high degree of mosaicism in patients' tissues. While major mutations that have been expanded in many cognate cells are readily detected by sequencing, minor ones are overlaid with a large depth of non-mutated alleles and are not detected. However, cell cloning enables us to observe such cryptic mutations as well as major mutations. In the present study, we focused on a fibroblastic cell line that is derived from a patient diagnosed with xeroderma pigmentosum (XP), which is an autosomal recessive disorder caused by a deficiency in nucleotide excision repair. By making a list of somatic mutations, we can expect to see a characteristic pattern of mutations caused by the hereditary disorder. We cloned a cell by generating an iPS cell line and performed a whole-exome sequencing analysis of the progenitor and its iPS cell lines. Unexpectedly, we failed to find causal mutations in the XP-related genes, but we identified many other mutations including homozygous deletion of GSTM1 and GSTT1. In addition, we found that the long arm of chromosome 9 formed uniparental disomy in the iPS cell line, which was also confirmed by a structural mutation analysis using a SNP array. Type and number of somatic mutations were different from those observed in XP patients. Taken together, we conclude that the patient might be affected by a different type of the disorder and that some of the mutations that we identified here may be responsible for exhibiting the phenotype. Sequencing and SNP-array data have been submitted to SRA and GEO under accession numbers SRP059858 and GSE55520, respectively

Profiling ascidian promoters as the primordial type of vertebrate promoter

<p>Abstract</p> <p>Background</p> <p>CpG islands are observed in mammals and other vertebrates, generally escape DNA methylation, and tend to occur in the promoters of widely expressed genes. Another class of promoter has lower G+C and CpG contents, and is thought to be involved in the spatiotemporal regulation of gene expression. Non-vertebrate deuterostomes are reported to have a single class of promoter with high-frequency CpG dinucleotides, suggesting that this is the original type of promoter. However, the limited annotation of these genes has impeded the large-scale analysis of their promoters.</p> <p>Results</p> <p>To determine the origins of the two classes of vertebrate promoters, we chose <it>Ciona intestinalis</it>, an invertebrate that is evolutionarily close to the vertebrates, and identified its transcription start sites genome-wide using a next-generation sequencer. We indeed observed a high CpG content around the transcription start sites, but their levels in the promoters and background sequences differed much less than in mammals. The CpG-rich stretches were also fairly restricted, so they appeared more similar to mammalian CpG-poor promoters.</p> <p>Conclusions</p> <p>From these data, we infer that CpG islands are not sufficiently ancient to be found in invertebrates. They probably appeared early in vertebrate evolution via some active mechanism and have since been maintained as part of vertebrate promoters.</p

Gradual transition from mosaic to global DNA methylation patterns during deuterostome evolution

<p>Abstract</p> <p>Background</p> <p>DNA methylation by the Dnmt family occurs in vertebrates and invertebrates, including ascidians, and is thought to play important roles in gene regulation and genome stability, especially in vertebrates. However, the global methylation patterns of vertebrates and invertebrates are distinctive. Whereas almost all CpG sites are methylated in vertebrates, with the exception of those in CpG islands, the ascidian genome contains approximately equal amounts of methylated and unmethylated regions. Curiously, methylation status can be reliably estimated from the local frequency of CpG dinucleotides in the ascidian genome. Methylated and unmethylated regions tend to have few and many CpG sites, respectively, consistent with our knowledge of the methylation status of CpG islands and other regions in mammals. However, DNA methylation patterns and levels in vertebrates and invertebrates have not been analyzed in the same way.</p> <p>Results</p> <p>Using a new computational methodology based on the decomposition of the bimodal distributions of methylated and unmethylated regions, we estimated the extent of the global methylation patterns in a wide range of animals. We then examined the epigenetic changes <it>in silico </it>along the phylogenetic tree. We observed a gradual transition from fractional to global patterns of methylation in deuterostomes, rather than a clear demarcation between vertebrates and invertebrates. When we applied this methodology to six piscine genomes, some of which showed features similar to those of invertebrates.</p> <p>Conclusions</p> <p>The mammalian global DNA methylation pattern was probably not acquired at an early stage of vertebrate evolution, but gradually expanded from that of a more ancient organism.</p

Evolutionary implications of inversions that have caused intra-strand parity in DNA

Abstract Background Chargaff's rule of DNA base composition, stating that DNA comprises equal amounts of adenine and thymine (%A = %T) and of guanine and cytosine (%C = %G), is well known because it was fundamental to the conception of the Watson-Crick model of DNA structure. His second parity rule stating that the base proportions of double-stranded DNA are also reflected in single-stranded DNA (%A = %T, %C = %G) is more obscure, likely because its biological basis and significance are still unresolved. Within each strand, the symmetry of single nucleotide composition extends even further, being demonstrated in the balance of di-, tri-, and multi-nucleotides with their respective complementary oligonucleotides. Results Here, we propose that inversions are sufficient to account for the symmetry within each single-stranded DNA. Human mitochondrial DNA does not demonstrate such intra-strand parity, and we consider how its different functional drivers may relate to our theory. This concept is supported by the recent observation that inversions occur frequently. Conclusion Along with chromosomal duplications, inversions must have been shaping the architecture of genomes since the origin of life