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TABLE OF CONTENTS
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| February 2018 Volume 50, Issue 2 |
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 |  Editorial
Comment
News & Views
Brief Communications
Letters
Articles
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Evolutionary Systems Biology (11-13 April 2018)
This conference will provide a forum for scientists interested in applying systems and mechanistic approaches to understand evolution, especially those working at the interface of evolution, quantitative genetics, and systems biology.
Deadlines: Bursaries: 30 Jan, Abstracts: 13 Feb, Registration: 13 Mar |  | | |
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Editorial | |
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| Our shared history p159
doi:10.1038/s41588-018-0049-4 |
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Comment | |
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| DNA.Land is a framework to collect genomes and phenomes in the era of abundant genetic information pp160 - 165
Jie Yuan, Assaf Gordon, Daniel Speyer, Richard Aufrichtig, Dina Zielinski et al.
doi:10.1038/s41588-017-0021-8 |
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News & Views | |
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Brief Communications | |
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| Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes pp172 - 174
Niels Grarup, Ida Moltke, Mette K. Andersen, Maria Dalby, Kristoffer Vitting-Seerup et al.
doi:10.1038/s41588-017-0022-7
Individuals from a Greenlandic Inuit population with homozygous loss-of-function variants in ADCY3 (adenylate cyclase 3) have increased risk for obesity and type 2 diabetes. Carriers of rare ADCY3 variants in trans-ancestry populations also show increased association with type 2 diabetes. |
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Letters | |
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| Loss-of-function mutations in ADCY3 cause monogenic severe obesity pp175 - 179
Sadia Saeed, Amélie Bonnefond, Filippo Tamanini, Muhammad Usman Mirza, Jaida Manzoor et al.
doi:10.1038/s41588-017-0023-6
Genetic analysis of children with severe obesity identifies mutations in the ADCY3 gene (encoding adenylate cyclase 3). These variants are rare in public databases and affect the functional activity of the protein, indicating that ADCY3 is a potential pharmacological target for obesity treatment. |
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| Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity pp180 - 185
Jacqueline E. Siljee, Yi Wang, Adelaide A. Bernard, Baran A. Ersoy, Sumei Zhang et al.
doi:10.1038/s41588-017-0020-9
MC4R colocalizes with ADCY3 at primary cilia in hypothalamic neurons, and MC4R mutations associated with human obesity impair this localization. Inhibition of adenylyl cyclase signaling at primary cilia of neurons leads to increased body weight in mice. |
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| Transposon-derived small RNAs triggered by miR845 mediate genome dosage response in Arabidopsis pp186 - 192
Filipe Borges, Jean-Sébastien Parent, Frédéric van Ex, Philip Wolff, German Martínez et al.
doi:10.1038/s41588-017-0032-5
A conserved microRNA targets LTR retrotransposons in Arabidopsis pollen, stimulating epigenetically activated siRNAs in a dose-dependent manner through RNA Pol IV. These miR845b-dependent easiRNAs mediate the interploidy hybridization barrier that leads to seed abortion. |
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| Paternal easiRNAs regulate parental genome dosage in Arabidopsis pp193 - 198
German Martinez, Philip Wolff, Zhenxing Wang, Jordi Moreno-Romero, Juan Santos-González et al.
doi:10.1038/s41588-017-0033-4
Depletion of easiRNAs (epigenetically activated small interfering RNAs) relieves the triploid block reproduction barrier mediated by increased paternal ploidy in Arabidposis. Loss of RNA Pol IV blocks easiRNA formation and rescues triploid seeds. |
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Articles | |
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| Reconstructing an African haploid genome from the 18th century pp199 - 205
Anuradha Jagadeesan, Ellen D. Gunnarsdóttir, S. Sunna Ebenesersdóttir, Valdis B. Guðmundsdóttir, Elisabet Linda Thordardottir et al.
doi:10.1038/s41588-017-0031-6
Reconstructing the genome of an ancestor: 788 Icelanders are descended from a man who arrived there in 1802. 38% of his African mother's genome has now been reconstructed from their pedigree and the genomes and genotypes of current Icelanders up to 8 generations later. |
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| An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer pp206 - 218
Ming Chen, Jiangwen Zhang, Katia Sampieri, John G. Clohessy, Lourdes Mendez et al.
doi:10.1038/s41588-017-0027-2
This study shows that inactivation of Pml in the mouse prostate turns indolent Pten-null tumors into lethal metastatic disease. The authors identify an aberrant SREBP prometastatic lipogenic program and show that a high-fat diet induces lipid accumulation in prostate tumors and is sufficient to drive metastasis. |
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| Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer pp219 - 228
Jingjing Chen, Ilaria Guccini, Diletta Di Mitri, Daniela Brina, Ajinkya Revandkar et al.
doi:10.1038/s41588-017-0026-3
Inactivation of pyruvate dehydrogenase A1 (PDHA1), a subunit of the pyruvate dehydrogenase complex (PDC) regulating mitochondrial metabolism, inhibits lipid biosynthesis and prostate cancer development in mouse and human xenograft tumor models. |
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| Multi-trait analysis of genome-wide association summary statistics using MTAG pp229 - 237
Patrick Turley, Raymond K. Walters, Omeed Maghzian, Aysu Okbay, James J. Lee et al.
doi:10.1038/s41588-017-0009-4
MTAG is a new method for joint analysis of summary statistics from genome-wide association studies of different traits. Applying MTAG to summary statistics for depressive symptoms, neuroticism and subjective well-being increased discovery of associated loci as compared to single-trait analyses. |
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| Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming pp238 - 249
Ralph Stadhouders, Enrique Vidal, François Serra, Bruno Di Stefano, François Le Dily et al.
doi:10.1038/s41588-017-0030-7
The authors analyze time-resolved changes in genome topology, gene expression, transcription-factor binding, and chromatin state during iPSC generation. They conclude that 3D genome reorganization generally precedes gene expression changes and that removal of locus-specific topological barriers explains why pluripotency genes are activated sequentially during reprogramming. |
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| Genetic determinants and epigenetic effects of pioneer-factor occupancy pp250 - 258
Julie Donaghey, Sudhir Thakurela, Jocelyn Charlton, Jennifer S. Chen, Zachary D. Smith et al.
doi:10.1038/s41588-017-0034-3
Investigation of FOXA2, GATA4 and OCT4 binding across several cell types provides insights into the genetic determinants and epigenetic effects of pioneer-factor occupancy. The data suggest that FOXA2 samples most of its potential binding sites but is stabilized at only a subset of targets. |
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| Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate pp259 - 269
Alexandre Mayran, Konstantin Khetchoumian, Fadi Hariri, Tomi Pastinen, Yves Gauthier et al.
doi:10.1038/s41588-017-0035-2
Analysis of Pax7 dynamics during pituitary lineage specification shows that Pax7 binds rapidly at uniquely marked heterochromatin pioneer sites and initiates chromatin opening that remains stable after Pax7 withdrawal, with loss of DNA hypermethylation at pioneered enhancers. |
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| The sea lamprey germline genome provides insights into programmed genome rearrangement and vertebrate evolution pp270 - 277
Jeramiah J. Smith, Nataliya Timoshevskaya, Chengxi Ye, Carson Holt, Melissa C. Keinath et al.
doi:10.1038/s41588-017-0036-1
A new assembly of the sea lamprey germline genome identifies genomic regions that are systematically eliminated from somatic tissue during early development. Comparative analysis gives new insight into vertebrate evolution. |
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| Pan-genome analysis highlights the extent of genomic variation in cultivated and wild rice pp278 - 284
Qiang Zhao, Qi Feng, Hengyun Lu, Yan Li, Ahong Wang et al.
doi:10.1038/s41588-018-0041-z
A pan-genome dataset of the Oryza sativa–Oryza rufipogon species complex generated through deep sequencing and de novo genome assembly of 66 divergent accessions will be helpful in pinpointing new causal variants underlying complex traits and in promoting evolutionary and functional studies in rice. |
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| Genomes of 13 domesticated and wild rice relatives highlight genetic conservation, turnover and innovation across the genus Oryza pp285 - 296
Joshua C. Stein, Yeisoo Yu, Dario Copetti, Derrick J. Zwickl, Li Zhang et al.
doi:10.1038/s41588-018-0040-0
Genome assemblies of 13 domesticated and wild rice relatives reveal salient features of genome evolution across the genus Oryza, especially rapid species diversification and turnover of transposons. This study also releases a complete long-read assembly of IR 8 'Miracle Rice'. |
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| Bph6 encodes an exocyst-localized protein and confers broad resistance to planthoppers in rice pp297 - 306
Jianping Guo, Chunxue Xu, Di Wu, Yan Zhao, Yongfu Qiu et al.
doi:10.1038/s41588-018-0039-6
The study reports map-based cloning and functional analysis of Bph6, which is associated with resistance to planthoppers in rice. BPH6 localizes to the exocyst and interacts with OsEXO70E1, and suppression of OsExo70E1 expression decreases resistance in Bph6-NIL plants. |
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| Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis pp307 - 316
Francesc Coll, Jody Phelan, Grant A. Hill-Cawthorne, Mridul B. Nair, Kim Mallard et al.
doi:10.1038/s41588-017-0029-0
A GWAS of multi- and extensively drug-resistant tuberculosis using 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries identifies novel mutations associated with resistance. The capacity to detect resistance in particular to ethionamide, pyrazinamide, capreomycin, cycloserine and paraaminosalicylic acid was enhanced by inclusion of insertions and deletions. |
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