Statistical design and analysis of RNA sequencing data, pp. 405–416
Paul L. Auer and R. W. Doerge
Next-generation DNA sequencing applications are becoming quite common, especially for investigating transcriptomes, but relatively little statistical guidance for RNA sequencing data is available. This article reviews essential experimental design issues of RNA sequencing, offers ways to exploit the technology for experimental replication, and discusses statistical methods for analyzing the data.
Whole-genome profiling of mutagenesis in Caenorhabditis elegans, pp. 431–441
Stephane Flibotte, Mark L. Edgley, Iasha Chaudhry, Jon Taylor, Sarah E. Neil, Aleksandra Rogula, Rick Zapf, Martin Hirst, Yaron Butterfield, Steven J. Jones, Marco A. Marra, Robert J. Barstead and Donald G.Moerman
and
Analysis of multiple ethyl methanesulfonate-mutagenized Caenorhabditis elegans strains by whole-genome sequencing, pp. 417–430
Sumeet Sarin, Vincent Bertrand, Henry Bigelow, Alexander Boyanov, Maria Doitsidou, Richard Poole, Surinder Narula and Oliver Hobert
“Next-generation” DNA sequencing is offering unprecedented views of genomes. These two articles describe the use of whole-genome sequencing to answer key questions that arise following forward genetic screens in Caenorhabditis elegans, such as mutagen efficiency and the effectiveness of outcrossing. The results provide some surprises about the consequences of outcrossing mutagenized strains and genetic drift among lab strains.
Assessing the influence of adjacent gene orientation on the evolution of gene upstream regions in Arabidopsis thaliana, pp. 695–701
Fei He, Wei-Hua Chen, Sinéad Collins, Claudia Acquisti, Ulrike Goebel, Sebastian Ramos-Onsins, Martin J. Lercher and Juliette de Meaux
DNA sequence elements in promoters control the accurate time and place of expression for each gene. Many of these elements are located within a 500–1000 bp window upstream of coding sequences. This may cause conflict between flanking genes when they are oriented head-to-head on the chromosome. This article describes an investigation of the effect of the relative orientation of flanking genes on the evolutionary dynamics of intergenic regions. There is considerable variation across loci, and intergenic regions located between two start codons tend to be more constrained in evolution.
The effect of recent admixture on inference of ancient human population history, pp. 611–622
Kirk E. Lohmueller, Carlos D. Bustamante and Andrew G. Clark
Single nucleotide polymorphism (SNP) data can provide a window into population history. Since demographic models seldom capture the complexities of population history, the parameter estimates can be uncertain. As an example of this, these authors evaluate the effect of recent European admixture on the ability to estimate growth parameters from ancestral African populations. They show that different summaries of SNP data are sensitive to model misspecifications in different ways, suggesting that the effects of model misspecification need to be carefully evaluated when interpreting parameter estimates.
Accurate prediction of genetic values for complex traits by whole-genome resequencing, pp. 623–631
Theo Meuwissen and Mike Goddard
Genetic improvement of crops and livestock is aided by the ability to predict genetic values for complex traits. Personalized medicine will require the ability to predict an individual's risk for diseases and response to treatments. These authors explore the accuracy of these predictions using full genome sequences. They find that an accuracy of prediction of genetic value up to 0.97 for complex traits in humans and livestock is within reach. Such accurate predictions of genetic value will revolutionize genetic risk prediction in humans and genomic selection in livestock and crops.
Decreased energy metabolism extends life span in Caenorhabditis elegans without reducing oxidative damage, pp. 559–571
Jeremy Michael Van Raamsdonk, Yan Meng, Darius Camp, Wen Yang, Xihua Jia, Claire Bénard and Siegfried Hekimi
The rate-of-living theory of aging posits that life span is determined by metabolic rate. The oxidative stress theory of aging proposes that this longevity results from decreased production of toxic reactive oxygen species (ROS). These authors describe 10 mutations that slow development and behavior and prolong life span of Caenorhabditis elegans by decreasing energy metabolism. However, they find no evidence for decreased ROS levels in these mutants, and most strains have increased sensitivity to ROS. Thus, decreased energy metabolism can lead to long life despite a normal or high level of oxidative stress.
A strand invasion 3′ polymerization intermediate of mammalian homologous recombination, pp. 443–457
Weiduo Si, Maureen M. Mundia, Alissa C. Magwood, Adam L. Mark, Richard D. McCulloch and Mark D. Baker
Repair of DNA double-stranded breaks by homologous recombination involves homology searching, 3′ strand invasion, and DNA synthesis. Little is known about these early events in mammalian cells. These authors exploit a plasmid:chromosome homologous recombination assay to characterize the new DNA synthesis that accompanies the homology search and strand invasion steps of mammalian homologous recombination. Genetic analysis of this system is expected to help reveal how defects in the early events of homologous recombination contribute to genome instability and cancer.
Feed-forward regulation of a cell fate determinant by an RNA-binding protein generates asymmetry in yeast, pp. 513–522
Joshua J. Wolf, Robin D. Dowell, Shaun Mahony, Michal Rabani, David K. Gifford and Gerald R. Fink
How is asymmetric cell division achieved? The transition between yeast and filamentous growth in Saccharomyces cerevisiae requires an asymmetric cell division: a yeast form mother cell gives rise to a filamentous daughter cell, or vice versa. This article describes experiments that show that transcriptional and translational repression of FLO11, which encodes a cell wall protein required for filamentous growth, by the RNA binding protein Khd1 controls expression of this cell fate determinant in the daughter cell. Feed-forward regulation generates the asymmetric FLO11 expression required for cells to enter and exit filamentous growth.