• Article |

    Genomic analyses of human populations in the Pacific provide insights into the peopling history of the region and reveal episodes of biological adaptation relating to the immune system and lipid metabolism through introgression from archaic hominins and polygenic adaptation.

    • Jeremy Choin
    • , Javier Mendoza-Revilla
    •  & Lluis Quintana-Murci
  • Article
    | Open Access

    The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

    • Daniel Taliun
    • , Daniel N. Harris
    •  & Gonçalo R. Abecasis
  • Article
    | Open Access

    Comparison of multiple genome assemblies from wheat reveals extensive diversity that results from the complex breeding history of wheat and provides a basis for further potential improvements to this important food crop.

    • Sean Walkowiak
    • , Liangliang Gao
    •  & Curtis J. Pozniak
  • Perspective
    | Open Access

    The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

    • Federico Abascal
    • , Reyes Acosta
    •  & Richard M. Myers
  • Article
    | Open Access

    A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.

    • Ryan L. Collins
    • , Harrison Brand
    •  & Michael E. Talkowski
  • Article
    | Open Access

    Using whole-genome sequencing data from 1,739 individuals, the GenomeAsia 100K Project catalogues genetic variation, population structure and disease associations to facilitate genetic studies in Asian populations and increase representation in genetics studies worldwide.

    • Jeffrey D. Wall
    • , Eric W. Stawiski
    •  & Andrew S. Peterson
  • Article
    | Open Access

    An improved, fully re-annotated Aedes aegypti genome assembly (AaegL5) provides insights into the sex-determining M locus, chemosensory systems that help mosquitoes to hunt humans and loci involved in insecticide resistance and will help to generate intervention strategies to fight this deadly disease vector.

    • Benjamin J. Matthews
    • , Olga Dudchenko
    •  & Leslie B. Vosshall
  • Article
    | Open Access

    Deep phenotype and genome-wide genetic data from 500,000 individuals from the UK Biobank, describing population structure and relatedness in the cohort, and imputation to increase the number of testable variants to 96 million.

    • Clare Bycroft
    • , Colin Freeman
    •  & Jonathan Marchini
  • Article
    | Open Access

    Whole-genome sequencing of 1,011 natural isolates of the yeast Saccharomyces cerevisiae reveals its evolutionary history, including a single out-of-China origin and multiple domestication events, and provides a framework for genotype–phenotype studies in this model organism.

    • Jackson Peter
    • , Matteo De Chiara
    •  & Joseph Schacherer
  • Letter
    | Open Access

    WebComparing the whole genome sequence of Apostasia shenzhenica with transcriptome and genome data from five orchid subfamilies permits the reconstruction of an ancestral gene toolkit, providing insight into orchid origins, evolution and diversification.

    • Guo-Qiang Zhang
    • , Ke-Wei Liu
    •  & Zhong-Jian Liu
  • Letter |

    Whole-genome sequencing of normal blood cells sampled from 241 adults is used to infer mosaic point mutations that are likely to have arisen during early embryogenesis, providing insight into how early cellular dynamics may affect adult tissues.

    • Young Seok Ju
    • , Inigo Martincorena
    •  & Michael R. Stratton
  • Article
    | Open Access

    Here, the genome sequence of the tiger tail seahorse is reported and comparative genomic analyses with other ray-finned fishes are used to explore the genetic basis of the unique morphology and reproductive system of the seahorse.

    • Qiang Lin
    • , Shaohua Fan
    •  & Byrappa Venkatesh
  • Article
    | Open Access

    Genomic and molecular analyses of Clunio marinus timing strains suggest that modulation of alternative splicing of Ca2+/calmodulin-dependent kinase II represents a mechanism for evolutionary adaptation of circadian timing.

    • Tobias S. Kaiser
    • , Birgit Poehn
    •  & Kristin Tessmar-Raible
  • Letter
    | Open Access

    De novo assembly and phasing of the genome of an individual from Korea using a combination of different sequencing approaches provides a useful population-specific reference genome and represents the most contiguous human genome assembly so far.

    • Jeong-Sun Seo
    • , Arang Rhie
    •  & Changhoon Kim
  • Article |

    Deep whole-genome sequencing of 300 individuals from 142 diverse populations provides insights into key population genetic parameters, shows that all modern human ancestry outside of Africa including in Australasians is consistent with descending from a single founding population, and suggests a higher rate of accumulation of mutations in non-Africans compared to Africans since divergence.

    • Swapan Mallick
    • , Heng Li
    •  & David Reich
  • Article |

    Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

    • Christian Fuchsberger
    • , Jason Flannick
    •  & Mark I. McCarthy
  • Article
    | Open Access

    The genome sequence is presented for the Atlantic salmon (Salmo salar), providing information about a rediploidization following a salmonid-specific whole-genome duplication event that resulted in an autotetraploidization.

    • Sigbjørn Lien
    • , Ben F. Koop
    •  & William S. Davidson
  • Article |

    It is known that there was gene flow from Neanderthals to modern humans around 50,000 years ago; now, analysis of a Neanderthal genome from the Altai Mountains in Siberia reveals evidence of gene flow 100,000 years ago in the other direction—from early modern humans to Neanderthals.

    • Martin Kuhlwilm
    • , Ilan Gronau
    •  & Sergi Castellano
  • Letter
    | Open Access

    Whole-genome sequencing of the seagrass Zostera, representing the first marine angiosperm genome to be fully sequenced, provides insight into the evolutionary changes associated with a transition to a marine environment in this angiosperm lineage.

    • Jeanine L. Olsen
    • , Pierre Rouzé
    •  & Yves Van de Peer
  • Letter |

    A large-scale enhancer complementation assay assessing the activating or repressing contributions of over 800 Drosophila transcription factors and cofactors to combinatorial enhancer control reveals a more complex picture than expected, with many factors having diverse regulatory functions that depend on the enhancer context.

    • Gerald Stampfel
    • , Tomáš Kazmar
    •  & Alexander Stark
  • Article
    | Open Access

    The Structural Variation Analysis Group of The 1000 Genomes Project reports an integrated structural variation map based on discovery and genotyping of eight major structural variation classes in 2,504 unrelated individuals from across 26 populations; structural variation is compared within and between populations and its functional impact is quantified.

    • Peter H. Sudmant
    • , Tobias Rausch
    •  & Jan O. Korbel
  • Letter |

    Human population genomic studies, including whole‐genome sequencing, were undertaken to identify determinants of bone mineral density (BMD), a major predictor of osteoporotic fractures. Non‐coding variants with large effects on BMD and fractures were identified near the EN1 locus and mouse studies confirmed this gene has an important role in skeletal biology.

    • Hou‐Feng Zheng
    • , Vincenzo Forgetta
    •  & J. Brent Richards
  • Letter
    | Open Access

    Octopus bimaculoides genome and transcriptome sequencing demonstrated that a core gene repertoire broadly similar to that of other invertebrate bilaterians is accompanied by expansions in the protocadherin and C2H2 zinc-finger transcription factor families and large-scale genome rearrangements closely associated with octopus-specific transposable elements.

    • Caroline B. Albertin
    • , Oleg Simakov
    •  & Daniel S. Rokhsar
  • Letter |

    A genome-wide analysis of 69 ancient Europeans reveals the history of population migrations around the time that Indo-European languages arose in Europe, when there was a large migration into Europe from the Eurasian steppe in the east (providing a genetic ancestry still present in Europeans today); these findings support a ‘steppe origin’ hypothesis for how some Indo-European languages arose.

    • Wolfgang Haak
    • , Iosif Lazaridis
    •  & David Reich
  • Letter |

    Single-molecule, real-time DNA sequencing is used to analyse a haploid human genome (CHM1), thus closing or extending more than half of the remaining 164 euchromatic gaps in the human genome; the complete sequences of euchromatic structural variants (including inversions, complex insertions and tandem repeats) are resolved at the base-pair level, suggesting that a greater complexity of the human genome can now be accessed.

    • Mark J. P. Chaisson
    • , John Huddleston
    •  & Evan E. Eichler
  • Letter |

    The authors show that two primate-specific genes encoding KRAB domain containing zinc finger proteins, ZNF91 and ZNF93, have evolved during the last 25 million years to repress retrotransposon families that emerged during this time period; according to the new data KZNF gene expansion limits the activity of newly emerged retrotransposons, which subsequently mutate to evade repression.

    • Frank M. J. Jacobs
    • , David Greenberg
    •  & David Haussler
  • Article
    | Open Access

    The genome of the gibbon, a tree-dwelling ape from Asia positioned between Old World monkeys and the great apes, is presented, providing insights into the evolutionary history of gibbon species and their accelerated karyotypes, as well as evidence for selection of genes such as those for forelimb development and connective tissue that may be important for locomotion through trees.

    • Lucia Carbone
    • , R. Alan Harris
    •  & Richard A. Gibbs
  • Letter
    | Open Access

    A reference genome from the coccolithophore Emiliania huxleyi is presented, along with sequences from 13 additional isolates, revealing a pan genome comprising core genes and genes variably distributed between strains: E. huxleyi is found to harbour extensive genetic variability under different metabolic repertoires, explaining its ability to thrive under a diverse range of environmental conditions.

    • Betsy A. Read
    • , Jessica Kegel
    •  & Igor V. Grigoriev
  • Letter
    | Open Access

    The genome of the carnivorous bladderwort plant Utricularia gibba is described here; despite having undergone at least three rounds of whole-genome duplication, its genome is unusually small and virtually devoid of intergenic DNA.

    • Enrique Ibarra-Laclette
    • , Eric Lyons
    •  & Luis Herrera-Estrella
  • Letter
    | Open Access

    The genome sequence and its analysis of the diploid wild wheat Triticum urartu (progenitor of the wheat A genome) represent a tool for studying the complex, polyploid wheat genomes and should be a valuable resource for the genetic improvement of wheat.

    • Hong-Qing Ling
    • , Shancen Zhao
    •  & Jun Wang
  • Article |

    Candida albicans is a prominent human fungal pathogen that until now was thought to be an obligate diploid; here it is shown that C. albicans can form viable haploids, that these haploids are able to mate to form heterozygous diploids, and that haploids and their auto-diploids are significantly less fit in vitro and in vivo than heterozygous progenitors or diploids formed by haploid mating pairs.

    • Meleah A. Hickman
    • , Guisheng Zeng
    •  & Judith Berman
  • Article |

    Nuclear genome transfer using unfertilized donor oocytes is performed and shown to be effective in preventing the transmission of mitochondrial DNA mutations; the swapped oocytes can develop to the blastocyst stage, and produce parthenogenetic embryonic stem-cell lines that show normal karyotypes and only mitochondrial DNA from the donor oocyte.

    • Daniel Paull
    • , Valentina Emmanuele
    •  & Dieter Egli
  • Article |

    A framework for metagenomic variation analysis to explore variation in the human microbiome is developed; the study describes SNPs, short indels and structural variants in 252 faecal metagenomes of 207 individuals from Europe and North America.

    • Siegfried Schloissnig
    • , Manimozhiyan Arumugam
    •  & Peer Bork
  • Letter |

    Resequencing of genes from individuals of European and African American ancestry indicates that approximately 73% of all protein-coding SNVs and approximately 86% of SNVs predicted to be deleterious arose in the past 5,000–10,000 years, and that European Americans carry an excess of deleterious variants in essential and Mendelian disease genes compared to African Americans.

    • Wenqing Fu
    • , Timothy D. O’Connor
    •  & Joshua M. Akey
  • Article |

    Mutations in mitochondrial DNA cause a wide range of disorders in humans, with a high prevalence; here it is shown that the nucleus of an affected woman’s egg could be inserted into healthy donor egg cytoplasm by spindle transfer, allowing the birth of healthy offspring.

    • Masahito Tachibana
    • , Paula Amato
    •  & Shoukhrat Mitalipov
  • Article
    | Open Access

    This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

    • Ian Dunham
    • , Anshul Kundaje
    •  & Ewan Birney
  • Letter
    | Open Access

    Chromosome conformation capture carbon copy (5C) is used to look at the relationships between functional elements and distal target genes in 1% of the human genome in three dimensions; the study describes numerous long-range interactions between promoters and distal sites that include elements resembling enhancers, promoters and CTCF-bound sites, their genomic distribution and complex interactions.

    • Amartya Sanyal
    • , Bryan R. Lajoie
    •  & Job Dekker
  • Article
    | Open Access

    Medulloblastoma is the most common malignant brain tumour in children; having assembled over 1,000 samples the authors report that somatic copy number aberrations are common in medulloblastoma, in particular a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is restricted to subgroup 4α, and translocations of PVT1, which are restricted to Group 3.

    • Paul A. Northcott
    • , David J. H. Shih
    •  & Michael D. Taylor