Transgenic Caenorhabditis elegans expressing a vav-1 mCherry transcriptional reporter in a live animal. vav-1 is expressed in pharyngeal tissue, a small subset of neurons, including ALA, spermatheca, vulva and rectal epithelia. VAV-1 acts in the ALA neuron to promote sleep-like behavior. See Fry et al. in this issue. Image courtesy of Amanda Fry and Ken Norman.

Check out the the March issue of GENETICS by looking at the highlights or the full table of contents!

This Month’s Centennial Articles

Richard Hudson and Norman Kaplan on the coalescent process, pp. 865–866

Nicholas H. Barton

Senior Editor Nicholas H. Barton introduces Hudson and Kaplan’s 1988 Classic, which extended the coalescent process to include selection, applying it to analyze sequence variation around the alcohol dehydrogenase locus of Drosophila melanogaster.

L.C. Dunn and Donald Charles on quantitative traits in the mouse, pp. 867–868

John C. Schimenti

Senior Editor John C. Schimenti introduces Dunn and Charles’ 1937 Classic on the highly variable coat patterns of the mouse. This remarkable work provides a window into the history of mouse genetics and quantitative trait studies at a time when little was known about the underlying mechanics.

Mutation and human exceptionalism: our future genetic load, pp. 869–875

Michael Lynch

Michael Lynch considers mutation rates in humans and the long-term consequences of a relaxation of selection against mildly deleterious mutations, including those magnifying the mutation rate itself. He argues these effects could become poten- tially measurable on the time scale of a few generations in westernized societies.

Is continued genetic improvement of livestock sustainable? pp. 877–881

William G. Hill

Large genetic improvements in many quantitative traits of livestock have been made over recent decades, and by introduction of genomic technology these are being enhanced. William G. Hill considers whether there is sufficient genetic variation to sustain such rapid rates of improvement in the future.

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MicroRNA biogenesis and hedgehog-patched signaling cooperate to regulate an important developmental transition in granule cell development, pp. 1105–1118

Lena Constantia, Myrna Constantin, and Brandon J. Wainwright

Cellular pathway interactions can be complex and unpredictable. The authors disrupted two distinct cellular pathways in granule cells of the cerebellum in Mus musculus. These pathways regulate the opposing growth processes of cellular attenuation and expansion to produce a developmentally stunted cerebellum or cancer. Surprisingly, combined pathway disruption did not bring the cerebellum towards growth equilibrium, but instead exasperated both phenotypes. Further, some genotypes displayed both extremes of the growth spectrum – hypoplasia and cancer – a signifier for a developmental transition. This work demonstrates how changes to the functional dosage of cellular pathways can produce unpredictable and extreme differences between siblings.

A conserved GEF for Rho-family GTPases acts in an EGF signaling pathway to promote sleep-like quiescence in Caenorhabditis elegans, pp. 1153–1166

Amanda L. Fry, Jocelyn T. Laboy, Huiyan Huang, Anne C. Hart, and Kenneth R. Norman

Despite being a subject of formal study for over 150 years, the molecular mechanisms underlying sleep are not well understood. Caenorhabditis elegans exhibits sleep-like behavioral quiescence, providing a valuable model system. Using genetic, molecular and behavioral approaches, Fry et al. show that C. elegans sleep-like quiescence is promoted by VAV-1, a conserved Rho GTPase guanine nucleotide exchange factor, by acting in a single interneuron to mediate EGF signaling. Importantly, vav-1 mutants fail to undergo sleep-like behavior after cellular stress, which leads to decreased organismal survival.

Collective fluctuations in the dynamics of adaptation and other traveling waves, pp. 1201–1227

Oskar Hallatschek and Lukas Geyrhofer

Ecological and evolutionary outcomes often depend on the behavior of a small number of leading “pioneers”. Examples are the dynamics of adaptation, epidemics, or species invasions. Hallatschek and Geyrhofer describe how large scale fluctuations emerge at the population level from chance events occurring in the pioneer population. The results can be used to predict, for instance, the decay of genetic diversity or variations in repeated evolution experiments.

Small heat shock proteins are novel common determinants of alcohol and nicotine sensitivity in Caenorhabditis elegans, pp. 1013–1027

James R. Johnson, Dayani Rajamanoharan, Hannah V. McCue, Kim Rankin, and Jeff W. Barclay

Although alcohol and nicotine have distinct effects within the brain, addiction to these and other drugs is associated with common genetic factors. Johnson et al. characterized a novel genetic pathway that determines sensitivity to alcohol and nicotine in Caenorhabditis elegans, a model organism with substance dose-dependent responses similar to mammals. The results identify a single cellular factor that can alter the neurological effects of diverse addictive substances.

Static and dynamic factors limit chromosomal replication complexity in Escherichia coli, avoiding dangers of runaway overreplication, pp. 945–960

Sharik R. Khan, Tulip Mahaseth, Elena A. Kouzminova, Glen E. Cronan, and Andrei Kuzminov

During chromosomal replication, there are exactly twice as many copies of the replicated regions as unreplicated ones in the same chromosome. This ratio is the “replication complexity index”. Bacterial cells can increase this ratio to four, but what is the actual limit of replication complexity? By using replication-inhibiting conditions or mutants, as well as inducible replication origins, these authors show that Escherichia coli cells can easily maintain three replication rounds per chromosome, can still grow slowly when pushed to four to five rounds, and can survive transient induction of six rounds per chromosome.

Hedgehog signaling strength is orchestrated by the mir-310 cluster of microRNAs in response to diet, pp. 1167–1183

Ibrahim Ömer Gifek, Samir Karaca, Marko Brankatschk, Suzanne Eaton, Henning Urlaub, and Halyna R. Shcherbata

Çiçek et al. show that nutritional status in Drosophila is perceived and interpreted via miRNAs. To ensure a fast and robust dietary response, the mir-310s target multiple genes associated with Hedgehog (Hh) signaling. The authors show that one of these targets, Rab23, is a novel component of Drosophila Hh signaling and cell-autonomously regulates Hh ligand trafficking in the stem cell niche in response to diet. They propose that targeting of several components of the same pathway is a crucial principle of miRNA-based regulation in unfavorable conditions.

Genomic patterns of geographic differentiation in Drosophila simulans, pp. 1229–1240

Alisa Sedghifar, Perot Saelao, and David J. Begun

Geographic patterns of genetic variation provide a rich source of information about population history. Sedghifar et al. compare and contrast patterns of differentiation in Drosophila simulans on two continents. The findings provide insights into geographic variation in D. simulans and how populations have been adapting to local environments since colonization of North America and Australia.

Local anesthetics and antipsychotic phenothiazines interact nonspecifically with membranes and inhibit hexose transporters in yeast, pp. 997–1012

Yukifumi Uesono, Akio Toh-e, Yoshiko Kikuchi, Tomoyuki Araki, Takushi Hachiya, Chihiro K. Watanabe, Ko Noguchi, and Ichiro Terashima

The mechanism of action of anesthetics remains unclear because it is unknown why structurally different drugs cause similar effects. Uesono et al. show that in yeast, local anesthetics and phenothiazines induced responses similar to glucose starvation. These drugs inhibited glucose uptake, but additional hexoses alleviated drug-induced effects via hexose transporters. The results suggest nonspecific interactions between membranes and the structurally distinct drugs preferentially inhibit the most abundant hexose transporters.

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