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Peter Chisnell, T Richard Parenteau, Elizabeth Tank, Kaveh Ashrafi, Cynthia Kenyon
The widely conserved heat-shock response, regulated by heat-shock transcription factors, is not only essential for cellular stress resistance and adult longevity, but also for proper development. However, the genetic mechanisms by which heat-shock transcription factors regulate development are not well understood. In C. elegans , we conducted an unbiased genetic screen to identify mutations that could ameliorate the developmental-arrest phenotype of a heat-shock factor mutant. Here we show that loss of the conserved translational activator rsks-1/ S6 Kinase, a downstream effector of mTOR kinase, can rescue the developmental-arrest phenotype of hsf-1 partial loss-of-function mutants...
September 18, 2018: Genetics
Jeremy Kreher, Teruaki Takasaki, Chad Cockrum, Simone Sidoli, Benjamin A Garcia, Ole N Jensen, Susan Strome
Epigenetic information contributes to proper gene expression and development and can be transmitted not only through mitotic divisions but also from parents to progeny. We investigated the roles in epigenetic inheritance of MES-4 and MET-1, the two Caenorhabditis elegans enzymes that methylate H3K36. Mass spectrometry analysis confirmed immunostaining results showing that both MES-4 and MET-1 catalyze H3K36me3. In the adult germline, MES-4 is enriched in the distal mitotic zone and MET-1 enriched in the meiotic pachytene zone...
September 14, 2018: Genetics
J Lucas Boatwright, Lauren M McIntyre, Alison M Morse, Sixue Chen, Mi-Jeong Yoo, Jin Koh, Pamela S Soltis, Douglas E Soltis, W Brad Barbazuk
Polyploidy has played a pivotal and recurring role in angiosperm evolution. Allotetraploids arise from hybridization between species and possess duplicated gene copies (homeologs) that serve redundant roles immediately after polyploidization. Although polyploidization is a major contributor to plant evolution, it remains poorly understood. We describe an analytical approach for assessing homeolog-specific expression that begins with de novo assembly of parental transcriptomes and effectively (i) reduces redundancy in de novo assemblies, (ii) identifies putative orthologs, (iii) isolates common regions between orthologs, and (iv) assesses homeolog-specific expression using a robust Bayesian Poisson-Gamma model to account for sequence bias when mapping polyploid reads back to parental references...
September 13, 2018: Genetics
Gregoriy A Dokshin, Krishna S Ghanta, Katherine M Piscopo, Craig C Mello
CRISPR-based genome editing using ribonucleoprotein (RNP) complexes and synthetic single stranded oligodeoxynucleotide (ssODN) donors can be highly effective. However, reproducibility can vary, and precise, targeted integration of longer constructs - such as green fluorescent protein (GFP) tags remains challenging in many systems. Here we describe a streamlined and optimized editing protocol for the nematode C. elegans. We demonstrate its efficacy, flexibility, and cost-effectiveness by affinity-tagging all twelve of 28 the Worm-specific Argonaute (WAGO) proteins in C...
September 13, 2018: Genetics
Paloma Medina, Bryan Thornlow, Rasmus Nielsen, Russell Corbett-Detig
Admixture, the mixing of genetically distinct populations, is increasingly recognized as a fundamental biological process. One major goal of admixture analyses is to estimate the timing of admixture events. Whereas most methods today can only detect the most recent admixture event, here we present coalescent theory and associated software that can be used to estimate the timing of multiple admixture events in an admixed population. We extensively validate this approach and evaluate the conditions under which it can successfully distinguish one from two-pulse admixture models...
September 11, 2018: Genetics
Caroline A Spike, Gabriela Huelgas-Morales, Tatsuya Tsukamoto, David Greenstein
In the nematode Caenorhabditis elegans , the conserved LIN-41 RNA-binding protein is a translational repressor that coordinately controls oocyte growth and meiotic maturation. LIN-41 exerts these effects, at least in part, by preventing the premature activation of the cyclin-dependent kinase CDK-1. Here we investigate the mechanism by which LIN-41 is rapidly eliminated upon the onset of meiotic maturation. Elimination of LIN-41 requires the activities of CDK-1 and multiple SCF (Skp1, Cul1, and F-box protein)-type E3 ubiquitin ligase subunits, including the conserved substrate adaptor protein SEL-10/Fbw7/Cdc4, suggesting that LIN-41 is a target of ubiquitin-mediated protein degradation...
September 11, 2018: Genetics
Sophie Maisnier-Patin, John R Roth
In the Cairns-Foster adaptive mutation system, a +1 lac frameshift mutant of Escherichia coli is plated on lactose medium, where the non-dividing population gives rise to Lac+ revertant colonies during a week under selection. Reversion requires the mutant lac allele to be located on a conjugative F' lac plasmid that also encodes the error-prone DNA polymerase, DinB. Rare plated cells with multiple copies of the mutant F' lac plasmid initiate the clones that develop into revertants under selection. These initiator cells arise before plating, and their extra lac copies allow them to divide on lactose and produce identical F' lac -bearing daughter cells that can mate with each other...
September 7, 2018: Genetics
Nikhil Mishra, Hai Wei, Barbara Conradt
Caspases have functions other than in apoptosis. Here we report that C. elegans CED-3 Caspase regulates asymmetric cell division. Many of the 131 cells that are 'programmed' to die during C. elegans development are the smaller daughter of a neuroblast that divides asymmetrically by size and fate. We have previously shown that CED-3 Caspase is activated in such neuroblasts, and that before neuroblast division, a gradient of CED-3 Caspase activity is formed in a ced-1 MEGF10-dependent manner. This results in the non-random segregation of active CED-3 Caspase or 'apoptotic potential' into the smaller daughter...
September 7, 2018: Genetics
David Gerard, Luis Felipe Ventorim Ferrão, Antonio Augusto Franco Garcia, Matthew Stephens
Detecting and quantifying the differences in individual genomes (i.e. genotyping), plays a fundamental role in most modern bioinformatics pipelines. Many scientists now use reduced representation nextgeneration sequencing (NGS) approaches for genotyping. Genotyping diploid individuals using NGS is a well-studied eld and similar methods for polyploid individuals are just emerging. However, there are many aspects of NGS data, particularly in polyploids, that remain unexplored by most methods. Our contributions in this paper are four-fold: (i) We draw attention to, and then model, common aspects of NGS data: sequencing error, allelic bias, overdispersion, and outlying observations...
September 5, 2018: Genetics
Arneet L Saltzman, Mark W Soo, Reta Aram, Jeannie T Lee
Chromatin modifications, including methylation of histone H3 at lysine 27 (H3K27me) by the Polycomb group proteins, play a broadly conserved role in the maintenance of cell fate. Diverse <u>chr</u>omatin <u>o</u>rganization <u>mo</u>difier (chromo) domain proteins act as 'readers' of histone methylation states. However, understanding the functional relationships among chromo domains and their roles in the inheritance of gene expression patterns remains challenging. Here, we identify two chromo domain proteins, CEC-1 and CEC-6, as potential readers of H3K27me in C...
September 5, 2018: Genetics
Daniel Sigal, Jennifer N S Reid, Lindi M Wahl
We investigate the fate of de novo mutations that occur during the in-host replication of a pathogenic virus, predicting the probability that such mutations are passed on during disease transmission to a new host. Using influenza A virus as a model organism, we develop a life-history model of the within-host dynamics of the infection, deriving a multitype branching process with a coupled deterministic model to capture the population of available target cells. We quantify the fate of neutral mutations and mutations affecting five life-history traits: clearance, attachment, budding, cell death, and eclipse phase timing...
September 4, 2018: Genetics
Yan Chen, Yan Zhang, Zhicheng Dong, David W Ow
Appropriate subcellular localization of regulatory factors is critical for cellular function. Pap1, a nucleocytoplasmic shuttling transcription factor of Schizosaccharomyces pombe , is redox regulated for localization and anti-stress function. In this study, we find that overproduction of a peptide conjugate containing the nuclear export signal of Oxs1, a conserved eukaryotic protein that along with Pap1 regulates certain diamide responsive genes, can retain Pap1 in the nucleus prior to stress by competing for nuclear export...
September 4, 2018: Genetics
Pau Bellot, Gustavo de Los Campos, Miguel Pérez-Enciso
The genetic analysis of complex traits does not escape the current excitement around artificial intelligence, including a renewed interest in 'deep learning' (DL) techniques such as Multilayer Perceptrons (MLPs) and Convolutional Neural Networks (CNNs). However, the performance of DL for genomic prediction of complex human traits has not been comprehensively tested. To provide an evaluation of MLPs and CNNs, we used data from distantly related white Caucasian individuals (n ∼ 100k individuals, m ∼ 500k SNPs, k=1000) of the interim release of the UK biobank...
August 31, 2018: Genetics
Oskar Hallatschek
Evolutionary dynamics driven out of equilibrium by growth, expansion or adaptation often generate a characteristically skewed distribution of descendant numbers: The earliest, the most advanced or the fittest ancestors have exceptionally large number of descendants, which Luria and Delbrück called "jackpot" events. Here, I show that recurrent jackpot events generate a deterministic median bias favoring majority alleles, which is akin to positive frequency-dependent selection (proportional to the log-ratio of the frequencies of mutant and wild-type alleles)...
August 31, 2018: Genetics
Xiongtao Dai, Hao Wang, Hongye Zhou, Le Wang, Jan Dvořák, Jeffrey L Bennetzen, Hans-Georg Müller
Long Terminal Repeat-Retrotransposons (LTR-RTs) are a major component of all flowering plant genomes. To analyze the time-dynamics of LTR-RTs, we model the insertion rates of the 35 most abundant LTR-RT families in the genome of Ae. tauschii , one of the progenitors of wheat. Our model of insertion rate (birth) takes into account random variation in LTR divergence, and the deletion rate (death) of LTR-RTs. Modeling the death rate is crucial because ignoring it would underestimate insertion rates in the distant past...
August 29, 2018: Genetics
Louis Lello, Steven G Avery, Laurent Tellier, Ana I Vazquez, Gustavo de Los Campos, Stephen D H Hsu
We construct genomic predictors for heritable but extremely complex human quantitative traits (height, heel bone density, and educational attainment) using modern methods in high dimensional statistics (i.e., machine learning). The constructed predictors explain, respectively, ∼40, 20, and 9 percent of total variance for the three traits, in data not used for training. For example, predicted heights correlate ∼0.65 with actual height; actual heights of most individuals in validation samples are within a few cm of the prediction...
August 27, 2018: Genetics
Heidi M Blank, Michelle Callahan, Ioannis P E Pistikopoulos, Aggeliki O Polymenis, Michael Polymenis
The longer cells stay in particular phases of the cell cycle, the longer it will take these cell populations to increase. However, the above qualitative description has very little predictive value, unless it can be codified mathematically. A quantitative relation that defines the population doubling time (Td ) as a function of the time eukaryotic cells spend in specific cell cycle phases would be instrumental for estimating rates of cell proliferation and for evaluating introduced perturbations. Here, we show that in human cells the length of the G1 phase (TG1 ) regressed on Td with a slope of ≈0...
August 27, 2018: Genetics
Jonas Meisner, Anders Albrechtsen
We here present two methods for inferring population structure and admixture proportions in low depth next generation sequencing data. Inference of population structure is essential in both population genetics and association studies and is often performed using principal component analysis or clustering-based approaches. Next-generation sequencing methods provide large amounts of genetic data but are associated with statistical uncertainty for especially low depth sequencing data. Models can account for this uncertainty by working directly on genotype likelihoods of the unobserved genotypes...
August 21, 2018: Genetics
Ana Llopart, Evgeny Brud, Nikale Pettie, Josep M Comeron
Interactions among divergent elements of transcriptional networks from different species can lead to misexpression in hybrids through regulatory incompatibilities, some with the potential to generate sterility. While the possible contribution of faster-male evolution to this misexpression has been explored, the role of the hemizygous X chromosome (i.e., the dominance theory for transcriptomes) remains yet to be determined. Here we study genome-wide patterns of gene expression in females and males of Drosophila yakuba , D...
August 21, 2018: Genetics
Woojin Kim, Ryan S Underwood, Iva Greenwald, Daniel D Shaye
OrthoList, a compendium of Caenorhabditis elegans genes with human orthologs compiled in 2011 by a meta-analysis of four orthology-prediction methods, has been a popular tool for identifying conserved genes for research into biological and disease mechanisms. However, the efficacy of orthology prediction depends on the accuracy of gene model predictions, an ongoing process, and orthology-prediction algorithms have also been updated over time. Here we present OrthoList 2 (OL2), a new comparative genomic analysis between C...
August 17, 2018: Genetics
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