Background Redundancy is a common feature of genomes, presumably to ensure robust growth under different and changing conditions. Genome compaction, removing sequences nonessential for given conditions, provides a novel way to understand the core principles of life. The synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) system is a unique feature implanted in the synthetic yeast genome (Sc2.0), which is proposed as an effective tool for genome minimization. As the Sc2.0 project is nearing its completion, we have begun to explore the application of the SCRaMbLE system in genome compaction. Results We develop a method termed SCRaMbLE-based genome compaction (SGC) and demonstrate that a synthetic chromosome arm (synXIIL) can be efficiently reduced. The pre-introduced episomal essential gene array significantly enhances the compacting ability of SGC, not only by enabling the deletion of nonessential genes located in essential gene containing loxPsym units but also by allowing more chromosomal sequences to be removed in a single SGC process. Further compaction is achieved through iterative SGC, revealing that at least 39 out of 65 nonessential genes in synXIIL can be removed collectively without affecting cell viability at 30 °C in rich medium. Approximately 40% of the synthetic sequence, encoding 28 genes, is found to be dispensable for cell growth at 30 °C in rich medium and several genes whose functions are needed under specified conditions are identified. Conclusions We develop iterative SGC with the aid of eArray as a generic yet effective tool to compact the synthetic yeast genome.
Eukaryotic DNA methylation has been receiving increasing attention for its crucial epigenetic regulatory function. The recently developed single-molecule real-time (SMRT) sequencing technology provides an efficient way to detect DNA N6-methyladenine (6mA) and N4-methylcytosine (4mC) modifications at a single-nucleotide resolution. The family Rosaceae contains horticultural plants with a wide range of economic importance. However, little is currently known regarding the genome-wide distribution patterns and functions of 6mA and 4mC modifications in the Rosaceae. In this study, we present an integrated DNA 6mA and 4mC modification database for the Rosaceae (MDR, http://mdr.xieslab.org ). MDR, the first repository for displaying and storing DNA 6mA and 4mC methylomes from SMRT sequencing data sets for Rosaceae, includes meta and statistical information, methylation densities, Gene Ontology enrichment analyses, and genome search and browse for methylated sites in NCBI. MDR provides important information regarding DNA 6mA and 4mC methylation and may help users better understand epigenetic modifications in the family Rosaceae.
Human housekeeping genes are often confused with essential human genes, and several studies regard both types of genes as having the same level of evolutionary conservation. However, this is not necessarily the case. To clarify this, we compared the differences between human housekeeping genes and essential human genes with respect to four aspects: the evolutionary rate (dN/dS), protein sequence identity, single-nucleotide polymorphism (SNP) density and level of linkage disequilibrium (LD). The results showed that housekeeping genes had lower evolutionary rates, higher sequence identities, lower SNP densities and higher levels of LD compared with essential genes. Together, these findings indicate that housekeeping and essential genes are two distinct types of genes, and that housekeeping genes have a higher level of evolutionary conservation. Therefore, we suggest that researchers should pay careful attention to the distinctions between housekeeping genes and essential genes. Moreover, it is still controversial whether we should substitute human orthologs of mouse essential genes for human essential genes. Therefore, we compared the evolutionary features between human orthologs of mouse essential genes and human housekeeping genes and we got inconsistent results in long-term and short-term evolutionary characteristics implying the irrationality of simply replacing human essential genes with human orthologs of mouse essential genes.
Interaction between genetic and epigenetic mechanisms may lead to autoimmune diseases. The features of these diseases show familial aggregation. The generality and specificity are keys to studying pathogenesis and etiology of them. This research integrated data of genetics and epigenetics, to find disease-related genes based on the levels of expression and regulation, and explored then to the shared and specific mechanism of them by analyzing shared and specific pathways of common four autoimmune diseases, including Type 1 Diabetes Mellitus (T1D), Multiple Sclerosis (MS), Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). The results showed that Lysosome and Fc gamma R-mediated phagocytosis are shared pathways of the four diseases. It means that the occurrence and development of them may associate with lysosomes and phagocytosis. And there were 2 pathways are shared pathways of three diseases, ribosome pathway associated with susceptibility to MS, RA and SLE, and Pathogenic Escherichia coli infection associated with susceptibility to T1D, MS and RA; 9 pathways are shared pathways of two diseases. The corporate underlying causes of these diseases may be these shared pathways activated. Furthermore, we found that T1D-related specific pathways (Insulin signaling,etc.) were 9, MS (Proteasome,etc.) is also 9, RA and SLE is 10 and 6 respectively. These pathways could help us to reveal shared and specific mechanisms of the four diseases.
N 6 -methyladenine (6mA) DNA modification has been detected in several eukaryotic organisms, where it plays important roles in gene regulation and epigenetic memory maintenance. However, the genome-wide distribution patterns and potential functions of 6mA DNA modification in woodland strawberry (Fragaria vesca) remain largely unknown. Here, we examined the 6mA landscape in the F. vesca genome by adopting singlemolecule real-time sequencing technology and found that 6mA modification sites were broadly distributed across the woodland strawberry genome. The pattern of 6mA distribution in the long non-coding RNA was significantly different from that in proteincoding genes. The 6mA modification influenced the gene transcription and was positively associated with gene expression, which was validated by computational and experimental analyses. Our study provides new insights into the DNA methylation in F. vesca.
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