The April issue of GENETICS is out now! Check out the highlights below of the full Table of Contents here.

Nascent transcription affected by RNA polymerase IV in Zea mays, pp. 1107–1125

Karl F. Erhard Jr., Joy-El R. B. Talbot, Natalie C. Deans, Allison E. McClish, and Jay B. Hollick

RNA polymerase IV (Pol IV) is required for plant development, though few Pol IV-regulated targets are known. Erhard Jr. et al. combined mutant analysis with global run-on profiling to identify maize genes and transposons whose nascent transcription is affected by Pol IV. This first glimpse of genome-wide Pol IV transcription in higher plants is consistent with models in which Pol IV competes with Pol II for transcription of both coding and non-coding regions.

Dramatic enhancement of genome editing by CRISPR/Cas9 through improved guide RNA design, pp. 959–971

Behnom Farboud and Barbara J. Meyer

Success with genome editing by Cas9 has been limited by the inability to predict effective guide RNAs and DNA target sites. Farboud and Meyer describe and validate a strategy for C. elegans that reliably achieves a high frequency of precise genome editing for all targets tested in vivo. The key innovation was inclusion of a GG motif at the 3’ end of the guide RNA target-specific sequence.

An estimate of the average number of recessive lethal mutations carried by humans, pp. 1243–1254

Ziyue Gao, Darrel Waggoner, Matthew Stephens, Carole Ober, and Molly Przeworski

Existing estimates of the burden of recessive deleterious alleles in humans are based on the increased mortality in offspring of consanguineous couples. However, this approach is confounded by environmental effects related to inbreeding. Gao et al. instead used a catalogue of severe genetic diseases in a founder population with a communal lifestyle and a known pedigree. They estimate that each human carries on average 0.58 autosomal recessive alleles that, when homozygous, lead to sterility or death between birth and reproductive age.

Evolutionary and functional analysis of the invariant SWIM domain in the conserved Shu2/SWS1 protein family from Saccharomyces cerevisiae to Homo sapiens, pp.1023–1033

Stephen K. Godin, Camille Meslin, Faiz Kabbinavar, Dominique S. Bratton-Palmer, Christina Hornack, Michael J. Mihalevic, Kyle Yoshida, Meghan Sullivan, Nathan L. Clark, and Kara A. Bernstein

Godin et al. show that the yeast Shu complex is a conserved regulator of homologous recombination during mitosis and meiosis. They find that Shu2 and its human ortholog SWS1 are conserved in early eukaryotic lineages and all major model organisms. Mutations of the highly conserved SWIM domain result in impaired protein-protein interactions and reduced repair of meiotic and mitotic breaks. Shu2/SWS1 exhibit strong co-evolutionary signatures with meiotic proteins in yeast and fruit flies, suggesting this complex plays an important role in meiosis.

A novel paradigm for nonassociative long-term memory in Drosophila: predator-induced changes in oviposition behavior, pp. 1143–1157

Balint Z. Kacsoh, Julianna Bozler, Sassan Hodge, Mani Ramaswami, and Giovanni Bosco

Exposures to environmental stressors induce innate behavioral responses and can lead to new memory formation. Kacsoh et al. explore the genetic requirements for a unique form of nonassociative behavior in Drosophila where female flies respond to endoparasitoid predatory wasps by altering their oviposition behavior to lay eggs in food containing high levels of alcohol. The induced oviposition behavior can last for days, and persistence of the behavior requires a functional mushroom body and several known learning and memory genes. This natural, ecologically-relevant behavior serves as a new paradigm for nonassociative long-term memory.

The Drosophila Genome Nexus: a population genomic resource of 623 Drosophila melanogaster genomes, including 197 from a single ancestral range population, pp.1229–1241

Justin B. Lack, Charis M. Cardeno, Marc W. Crepeau, William Taylor, Russell B. Corbett-Detig, Kristian A. Stevens, Charles H. Langley, and John E. Pool

Hundreds of wild-derived D. melanogaster genomes have been published, but rigorous comparisons across data sets are precluded by differences in alignment methodology. Lacket al. reassembled previously published D. melanogaster population genomic data and added unpublished genomes from several sub-Saharan populations, totaling more than 600 genomes. Notably, they present aligned data from phase 3 of the Drosophila Population Genomics Project, which provides 197 genomes from a single ancestral range population.

The NuA4 complex promotes Translesion Synthesis (TLS)-mediated DNA damage tolerance, pp. 1065–1076

Margaret Renaud-Young, David C. Lloyd, Kate Chatfield-Reed, Iain George, Gordon Chua, and Jennifer Cobb

The DNA damage tolerance (DDT) pathway allows a replisome to bypass DNA lesions and complete S phase in the presence of unrepaired damage. Renaud-Young et al. identify the NuA4 histone acetyltransferase and its target, HTZ1, as functioning on the error-prone/Translesion Synthesis (TLS) branch of DDT. Restricting NuA4 activity to G2/M phase restored viability and TLS-dependent mutagenesis rates, indicating that the critical role of NuA4 in error-prone bypass is functional even after the bulk of replication is complete.

Bayesian network reconstruction using systems genetics data: comparison of MCMC methods, pp. 973–989

Shinya Tasaki, Ben Sauerwine, Bruce Hoff, Hiroyoshi Toyoshiba, Chris Gaiteri, and Elias Chaibub Neto

Reconstructing biological networks using high-throughput technologies has the potential to produce condition-specific interactomes. But are these reconstructed networks a reliable source of biological interactions? To identify reliable methods to generate these networks, Tasaki et al. conducted a large simulation study to attempt to recover such networks from realistic and known regulatory structures. The results identify existing and novel methods that can accurately reconstruct networks, as well as characteristics of raw data that can also affect reconstruction accuracy.


What do you mean, “epigenetic”?, pp. 887–896

Carrie Deans and Keith A. Maggert

Research in the field of epigenetics has increased exponentially over the last decade, with the number of articles using the term growing over 7-fold. Despite this exploding popularity, the field suffers from the inconsistent usage of the word “epigenetic”, stemming from its evolving association with genetic inheritance systems, unclear terminology, and a prioriexpectations or assumptions. This Perspectives discusses this history, documents the different interpretations of epigenetics, and highlights how different uses of the term have led to difficulties in integrating the field. The authors attempt to clarify its use by offering their own definition, and provide suggestions for addressing the conceptual and mechanistic problems this ambiguity has created.