http://genomebiology.com The latest research articles published by Genome Biology 2012-05-25T00:00:00Z A report on the Keystone symposium 'Non-coding RNAs' held at Snowbird, Utah, USA, 31 March to 5 April 2012. http://genomebiology.com/2012/13/5/315 Ezgi Hacisuleyman Moran Cabili John Rinn Genome Biology 2012, null:315 2012-05-25T00:00:00Z doi:10.1186/gb-2012-13-5-315 A Keystone for ncRNA John Rinn and colleagues give a report on the Keystone symposium 'Non-coding RNAs' held at Snowbird, Utah, USA, 31 March to 5 April 2012. /content/figures/gb-2012-13-5-315-toc.gif Genome Biology 1465-6906 ${item.volume} 315 2012-05-25T00:00:00Z XML Background: Little is known about the mechanisms of adaptation of life to the extreme environmental conditions encountered in polar regions. Here we present the genome sequence of a unicellular green alga from the division chlorophyta, Coccomyxa subellipsoidea C-169, which we will hereafter refer to as C-169. This is the first eukaryotic microorganism from a polar environment to have its genome sequenced. Results: The 48.8-Mb genome contained in 20 chromosomes exhibits significant synteny conservation with the chromosomes of its relatives Chlorella variabilis and Chlamydomonas reinhardtii. The order of the genes was highly reshuffled within synteny blocks suggesting that intra-chromosomal rearrangements were more prevalent than inter-chromosomal rearrangements. Remarkably, Zepp retrotransposons occur in clusters of nested elements with strictly one cluster per chromosome probably residing at the centromere. Several protein families overrepresented in C. subellipsoidae include proteins involved in lipid metabolism, transporters, cellulose synthases and short alcohol dehydrogenases. Conversely, C-169 lacks proteins that exist in all other sequenced chlorophytes, including components of the glycosyl phosphatidyl inositol anchoring system, pyruvate phosphate dikinase and the photosystem 1 reaction center subunit N (PsaN). Conclusions: We suggest that some of these gene losses and gains could have contributed to adaptation to low temperatures. Comparison of these genomic features with the adaptive strategies of psychrophilic microbes suggests that prokaryotes and eukaryotes followed comparable evolutionary routes to adapt to cold environments. http://genomebiology.com/2012/13/5/R39 Guillaume Blanc Irina Agarkova Jane Grimwood Alan Kuo Andrew Brueggeman David Dunigan James Gurnon Istvan Ladunga Erika Lindquist Susan Lucas Jasmyn Pangilinan Thomas Proschold Asaf Salamov Jeremy Schmutz Donald Weeks Takashi Yamada Jean-Michel Claverie Igor Grigoriev James Van Etten Alexandre Lomsadze Mark Borodovsky Genome Biology 2012, null:R39 2012-05-25T00:00:00Z doi:10.1186/gb-2012-13-5-r39 Polar alga genome The first genome of a polar eukaryotic microorganism, an alga called Coccomyxa subellipsoidea C-169, reveals universal strategies for cold adaptation /content/figures/gb-2012-13-5-r39-toc.gif Genome Biology 1465-6906 ${item.volume} R39 2012-05-25T00:00:00Z PDF Background: Entamoeba histolytica is a significant cause of disease worldwide. However, little is known about the genetic diversity of the parasite. We re-sequenced the genomes of ten laboratory cultured lines of the eukaryotic pathogen Entamoeba histolytica in order to develop a picture of genetic diversity across the genome. Results: The extreme nucleotide composition bias and repetitiveness of the E. histolytica genome provide a challenge for short-read mapping, yet we were able to define putative single nucleotide polymorphisms in a large portion of the genome. The results suggest a rather low level of single nucleotide diversity, although genes and gene families with putative roles in virulence are among the more polymorphic genes. We did observe large differences in coverage depth among genes, indicating differences in gene copy number between genomes. We found evidence indicating that recombination has occurred in the history of the sequenced genomes, suggesting that E. histolytica may reproduce sexually. Conclusions: E. histolytica displays a relatively low level of nucleotide diversity across its genome. However, large differences in gene family content and gene copy number are seen among the sequenced genomes. The pattern of polymorphism indicates that E. histolytica reproduces sexually, or has done so in the past, which has previously been suggested but not proven. http://genomebiology.com/2012/13/5/R38 Gareth Weedall Graham Clarck Pia Koldkjaer Suzanne Kay Iris Bruchhaus Egbert Tannich Steve Patterson Neil Hall Genome Biology 2012, null:R38 2012-05-25T00:00:00Z doi:10.1186/gb-2012-13-5-r38 Entamoeba histolytica diversity Ten strains of Entamoeba histolytica are sequenced. Low levels of genetic diversity are found, and evidence for sexual reproduction is uncovered /content/figures/gb-2012-13-5-r38-toc.gif Genome Biology 1465-6906 ${item.volume} R38 2012-05-25T00:00:00Z PDF Background: Elucidation of a genotype-phenotype relationship is critical to understand an organism at the whole-system level. Here, we demonstrate that comparative analyses of multi-omics data combined with a computational modeling approach provide a framework for elucidating the phenotypic characteristics of organisms whose genomes are sequenced. Results: We present a comprehensive analysis of genome-wide measurements incorporating multifaceted holistic data - genome, transcriptome, proteome, and phenome - to determine the differences between Escherichia coli B and K-12 strains. A genome-scale metabolic network of E. coli B was reconstructed and used to identify genetic bases of the phenotypes unique to B compared with K-12 through in silico complementation test. This systems analysis revealed that E. coli B was well-suited for production of recombinant proteins due to a greater capacity for amino acid biosynthesis, fewer proteases, and lack of flagella. Furthermore, E. coli B had an additional type II secretion system and a different cell wall and outer membrane composition predicted to be more favorable for protein secretion. In contrast, E. coli K-12 showed a higher expression of heat shock genes and was less susceptible to certain stress conditions. Conclusions: This integrative systems approach provides a high-resolution system-wide view and insights into why two closely related groups of E. coli B and K-12 manifest distinct phenotypes. Therefore, systematic understanding of cellular physiology and metabolism of the strains is essential not only to determine culture condition and, but also to design recombinant hosts. http://genomebiology.com/2012/13/5/R37 Sung Ho Yoon Mee-Jung Han Haeyoung Jeong Choong Hoon Lee Xiao-Xia Xia Dae-Hee Lee Ji Hoon Shim Sang Yup Lee Tae Kwang Oh Jihyun Kim Genome Biology 2012, null:R37 2012-05-25T00:00:00Z doi:10.1186/gb-2012-13-5-r37 Multi-omics systems analysis An analysis of multi-omics data and the generation of a genome-scale metabolic network to determine the phenotypic characteristics of E. coli /content/figures/gb-2012-13-5-r37-toc.gif Genome Biology 1465-6906 ${item.volume} R37 2012-05-25T00:00:00Z PDF Background: The major cell cycle control acting at the G2 to mitosis transition is triggered in all eukaryotes by cyclin-dependent kinases (CDKs). In the fission yeast Schizosaccharomyces pombe the activation of the G2/M CDK is regulated primarily by dephosphorylation of the conserved residue Tyr15 in response to the stress-nutritional response and cell geometry sensing pathways. To obtain a more complete view of the G2/M control we have screened systematically for gene deletions that advance cells prematurely into mitosis. Results: A screen of 82% of fission yeast non-essential genes, comprising approximately 3000 gene deletion mutants, identified 18 genes which act negatively at mitotic entry, 7 of which have not been previously described as cell cycle regulators. Eleven of the 18 genes function through the stress response and cell geometry sensing pathways, both of which pathways act through CDK Tyr15 phosphorylation, and 4 of the remaining genes regulate the G2/M transition by inputs from hitherto unknown pathways. Three genes act independently of CDK Tyr15 phosphorylation and define additional uncharacterized molecular control mechanisms. Conclusions: Despite extensive investigation of the G2/M control, our work has revealed new components of characterized pathways that regulate CDK Tyr15 phosphorylation and new components of novel mechanisms controlling mitotic entry. http://genomebiology.com/2012/13/5/R36 Francisco Navarro Paul Nurse Genome Biology 2012, null:R36 2012-05-24T00:00:00Z doi:10.1186/gb-2012-13-5-r36 Cell cycle control A screen for regulators of the G2/M transition in fission yeast reveals novel regulators of cell cycle control /content/figures/gb-2012-13-5-r36-toc.gif Genome Biology 1465-6906 ${item.volume} R36 2012-05-24T00:00:00Z PDF Background: Nonsense-mediated mRNA decay (NMD) affects the outcome of alternative splicing by degrading mRNA isoforms with premature termination codons. Splicing regulators constitute important NMD targets, however, the extent to which loss of NMD causes extensive deregulation of alternative splicing has not previously been assayed in a global, unbiased manner. Here, we combine mouse genetics and RNA-seq to provide the first in vivo analysis of the global impact of NMD on splicing patterns in two primary mouse tissues ablated for the NMD factor UPF2. Results: We developed a bioinformatic pipeline, which maps RNA-seq data to a combinatorial exon database, predicts NMD-susceptibility for mRNA isoforms and calculates the distribution of major splice isoform classes. We present a catalog of NMD-regulated alternative splicing events, showing that isoforms of 30% of all expressed genes are upregulated in NMD deficient cells and that NMD targets all major splicing classes. Importantly, NMD-dependent effects are not restricted to premature termination codon+ isoforms but also involve an abundance of splicing events that do not generate premature termination codons. Supporting their functional importance the latter events are associated with high intronic conservation. Conclusion: Our data demonstrate that NMD regulates alternative splicing outcomes through an intricate web of splicing regulators and that its loss leads to the deregulation of a panoply of splicing events, providing novel insights into its role in core- and tissue-specific regulation of gene expression. Thus, our study extends the importance of NMD from an mRNA quality pathway to a regulator of several layers of gene expression. http://genomebiology.com/2012/13/5/R35 Joachim Weischenfeldt Johannes Waage Geng Tian Jing Zhao Inge Damgaard Janus Jakobsen Karsten Kristiansen Anders Krogh Jun Wang Bo Porse Genome Biology 2012, null:R35 2012-05-24T00:00:00Z doi:10.1186/gb-2012-13-5-r35 NMD-dependent splicing An extensive in vivo analysis of how nonsense mediated mRNA decay regulates alternative splicing in two mouse tissues /content/figures/gb-2012-13-5-r35-toc.gif Genome Biology 1465-6906 ${item.volume} R35 2012-05-24T00:00:00Z PDF A genome-wide epigenetic analysis of enhancer elements in colon cancer has implicated distal gene regulatory DNA sequences in the establishment of an oncogenic transcriptional program. http://genomebiology.com/2012/13/5/156 Siavash Kurdistani Genome Biology 2012, null:156 2012-05-23T00:00:00Z doi:10.1186/gb4019 Cancer epigenomes A Research Highlight on the role of variant epigenetics in establishing an enhancer element-mediated oncogenic transcriptional program /content/figures/gb-2012-13-5-156-toc.gif Genome Biology 1465-6906 ${item.volume} 156 2012-05-23T00:00:00Z XML We propose a new method that incorporates population re-sequencing data, distribution of reads, and strand bias in detecting low-level mutations. The method can accurately identify low-level mutations down to a level of 2.3%, with an average coverage of 500x, and with a false discovery rate of less than 1%. In addition, we also discuss other problems in detecting low-level mutations, including chimeric reads and sample cross-contamination, and provide possible solutions to them. http://genomebiology.com/2012/13/5/R34 Mingkun Li Mark Stoneking Genome Biology 2012, null:R34 2012-05-23T00:00:00Z doi:10.1186/gb-2012-13-5-r34 Detecting low-level mutations A method is presented for differentiating mutations present at low level in a sample from sequencing errors /content/figures/gb-2012-13-5-r34-toc.gif Genome Biology 1465-6906 ${item.volume} R34 2012-05-23T00:00:00Z PDF A recent publication has provided a comprehensive atlas of gene expression profiles of 995 genes linked to neuronal functions in two regions of the human brain neocortex. http://genomebiology.com/2012/13/5/157 Philipp Khaitovich Genome Biology 2012, null:157 2012-05-22T00:00:00Z doi:10.1186/gb-2012-13-5-157 Brain transcriptomes Philipp Khaitovich highlights research by Allan Jones and colleagues that assesses regional gene expression in the human brain neocortex /content/figures/gb-2012-13-5-157-toc.gif Genome Biology 1465-6906 ${item.volume} 157 2012-05-22T00:00:00Z XML {no abstract}. http://genomebiology.com/2012/13/5/155 Gregory Petsko Genome Biology 2012, null:155 2012-05-18T00:00:00Z doi:10.1186/gb-2012-13-5-155 Goodbye, Columbus Guaranteeing experimental outcomes and findings: funding then and now /content/figures/gb-2012-13-5-155-toc.gif Genome Biology 1465-6906 ${item.volume} 155 2012-05-18T00:00:00Z XML