Population genetics

  • Article
    | Open Access

    Schizophrenia has been associated with increased risk of breast cancer, yet the risk of schizophrenia following breast cancer is unclear. Here, the authors show a bidirectional association between breast cancer and schizophrenia in Sweden and a shared genetic contribution to both diseases.

    • Donghao Lu
    • , Jie Song
    •  & Unnur A. Valdimarsdóttir
  • Article
    | Open Access

    Genetic variation in modern humans can reveal information about a population’s history and migration patterns. Here, the authors describe the ancestry and geospatial genetic structure of the Netherlands, and demonstrate the utility of haplotype-based covariates in genome-wide association studies.

    • Ross P. Byrne
    • , Wouter van Rheenen
    •  & Russell L. McLaughlin
  • Article
    | Open Access

    Pleistocene population dynamics can inform the consequences of current climate change. This phylogeography of 35 complete American mastodon mitochondrial genomes suggests distinct lineages in this species repeatedly expanded northwards and then went locally extinct in response to glacial cycles.

    • Emil Karpinski
    • , Dirk Hackenberger
    •  & Hendrik N. Poinar
  • Article
    | Open Access

    Structural genomic variation can fuel evolution. Here, authors present genome data from seven Corvus species and unearth structural variants that vary between incipient crow species in Europe, with implications for premating isolation involving plumage patterning.

    • Matthias H. Weissensteiner
    • , Ignas Bunikis
    •  & Jochen B. W. Wolf
  • Article
    | Open Access

    Evidence that somatic mutation rates in introns exceed those in exons challenges the molecular evolution tenet that mutation rate and sequence function are independent. Here, authors analyze germline de novo mutations and reveal no evidence for mutation rate differences between exons and introns.

    • Miguel Rodriguez-Galindo
    • , Sònia Casillas
    •  & Antonio Barbadilla
  • Article
    | Open Access

    Reduction of pollen grain number is widespread in selfing plants, but the determining gene is unknown. Here, the authors show that a ribosome-biogenesis factor encoding gene RDP1 is responsible for adaptive reduction of male gamete number in Arabidopsis thaliana.

    • Takashi Tsuchimatsu
    • , Hiroyuki Kakui
    •  & Kentaro K. Shimizu
  • Article
    | Open Access

    Multi-nucleotide variants (MNV) are genetic variants in close proximity of each other on the same haplotype whose functional impact is difficult to predict if they reside in the same codon. Here, Wang et al. use the gnomAD dataset to assemble a catalogue of MNVs and estimate their global mutation rate.

    • Qingbo Wang
    • , Emma Pierce-Hoffman
    •  & Daniel G. MacArthur
  • Article
    | Open Access

    Hybrid genomes provide a window into the speciation process over time. Here, Chaturvedi et al. use Lycaeides butterflies from hybrid zones of different ages to show that selection and recombination have repeatable effects on hybrid genome composition across timescales.

    • Samridhi Chaturvedi
    • , Lauren K. Lucas
    •  & Zachariah Gompert
  • Article
    | Open Access

    Sorting insects based on sex is error prone and frequently labour intensive. Here, the authors present a drug-inducible sex separation system based on sex-specific rescue from antibotic toxicity.

    • Nikolay P. Kandul
    • , Junru Liu
    •  & Omar S. Akbari
  • Article
    | Open Access

    Mutations in PTEN have been associated with various human disease, including autism spectrum disorder (ASD) and cancer. Here, the authors assess the function of 106 PTEN variants in yeast, invertebrate models and cell culture and report that PTEN variants generally decrease protein stability.

    • Kathryn L. Post
    • , Manuel Belmadani
    •  & Kurt Haas
  • Article
    | Open Access

    Empirical examples documenting the pace of adaptation across the whole genome in wild populations are scarce. Here the authors study wild stickleback populations from lake and stream habitats and show that there is a genome-wide signature of adaptation to stream habitats within just one generation.

    • Telma G. Laurentino
    • , Dario Moser
    •  & Daniel Berner
  • Article
    | Open Access

    European populations underwent strong genetic changes during the Neolithic. Here, Furtwängler et al. provide ancient nuclear and mitochondrial genomic data from the region of Switzerland during the end of the Neolithic and the Early Bronze Age that reveal a complex genetic turnover during the arrival of steppe ancestry.

    • Anja Furtwängler
    • , A. B. Rohrlach
    •  & Johannes Krause
  • Article
    | Open Access

    Polygenic scores are believed to hold future promise for trait prediction and personalized medicine, but are sensitive to demographic history. Here, Marnetto et al. develop partial polygenic scores supplemented with local ancestry deconvolution which improves prediction accuracy into recently admixed European populations.

    • Davide Marnetto
    • , Katri Pärna
    •  & Luca Pagani
  • Article
    | Open Access

    Population structure, even subtle differences within seemingly homogenous populations, can have an impact on the accuracy of polygenic prediction. Here, Sakaue et al. use dimensionality reduction methods to reveal fine-scale structure in the Biobank Japan cohort and explore the performance of polygenic risk scores.

    • Saori Sakaue
    • , Jun Hirata
    •  & Yukinori Okada
  • Article
    | Open Access

    In the Indo-Pacific, multiple Anguilla eel species overlap in their spawning. Here, the authors sequence three Anguilla genomes and with genome-wide data of four more congeners, investigate contemporary hybridization, historical introgression, and the maintenance of species boundaries despite substantial gene flow.

    • Julia M. I. Barth
    • , Chrysoula Gubili
    •  & Robert Schabetsberger
  • Article
    | Open Access

    CRISPR homing gene drives are highly invasive and can fail due to the rapid evolution of resistance. Here the authors present TARE drive, inspired by naturally occurring selfish genetic elements, which is less vulnerable to resistance and can potentially be confined to a target population.

    • Jackson Champer
    • , Esther Lee
    •  & Philipp W. Messer
  • Article
    | Open Access

    Ancient DNA analysis of early European farmers has found a high level of genetic affinity with present-day Sardinians. Here, the authors generate genome-wide capture data for 70 individuals from Sardinia spanning the Middle Neolithic to Medieval period to reveal relationships with mainland European populations shifting over time.

    • Joseph H. Marcus
    • , Cosimo Posth
    •  & John Novembre
  • Article
    | Open Access

    Although there is extensive theory predicting the effects of population bottlenecks on mutation load, there is little empirical evidence from recent bottlenecks. Here, Grossen et al. compare the consequences of population bottlenecks in six ibex species for genome-wide variation and mutation load.

    • Christine Grossen
    • , Frédéric Guillaume
    •  & Daniel Croll
  • Article
    | Open Access

    Dingoes evolved in isolation from both their domesticated and wild ancestors. Here, the authors investigate the genomic basis of the feralization of dingoes and trace their origin to domestic dogs that migrated to Australia approximately 8300 years ago.

    • Shao-jie Zhang
    • , Guo-Dong Wang
    •  & Ya-ping Zhang
  • Article
    | Open Access

    Few studies empirically pinpoint how balanced polymorphisms are maintained. “Mérot et al”. identify an inversion polymorphism that is maintained in seaweed fly populations because of antagonistic pleiotropy that mediates a classic life history tradeoff between larval survival and adult reproduction.

    • Claire Mérot
    • , Violaine Llaurens
    •  & Maren Wellenreuther
  • Article
    | Open Access

    Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

    • Pilar Cacheiro
    • , Violeta Muñoz-Fuentes
    •  & Coleen Kane
  • Article
    | Open Access

    Population-based association analyses of rare genetic variants with complex traits are limited by the availability of data from sufficiently large cohorts. Here, Cirulli et al. report gene-based collapsing analysis of exomes from 49,960 participants of the UK Biobank and 21,866 participants of the Healthy Nevada Project over a total of 4377 traits.

    • Elizabeth T. Cirulli
    • , Simon White
    •  & Nicole L. Washington
  • Article
    | Open Access

    G-quadruplexes (G4s) are secondary structures that can form in both DNA and RNA from guanine-rich sequences which are enriched in untranslated regions (UTRs). Here, Lee et al. find that putative G4-forming sequences are evolutionarily constrained, enriched for RNA-binding protein interactions and enriched for disease genetic associations.

    • David S. M. Lee
    • , Louis R. Ghanem
    •  & Yoseph Barash
  • Article
    | Open Access

    Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.

    • Mark Pinese
    • , Paul Lacaze
    •  & David M. Thomas
  • Article
    | Open Access

    RNA-sequencing is mostly used to assess gene expression; however, it can also give information about genetic variants. Here, the authors present CaSpER, a statistical framework that utilises RNA-sequencing reads to identify and visualise CNV events by integrating transcriptome-wide expression and allelic shift profiles.

    • Akdes Serin Harmanci
    • , Arif O. Harmanci
    •  & Xiaobo Zhou
  • Article
    | Open Access

    Birch pitch is thought to have been used in prehistoric times as hafting material or antiseptic and tooth imprints suggest that it was chewed. Here, the authors report a 5,700 year-old piece of chewed birch pitch from Denmark from which they successfully recovered a complete ancient human genome and oral microbiome DNA.

    • Theis Z. T. Jensen
    • , Jonas Niemann
    •  & Hannes Schroeder
  • Article
    | Open Access

    Relapse, reinfection and recrudescence can all cause recurrent infection after treatment of Plasmodium vivax malaria in endemic areas, but are difficult to distinguish. Here the authors show that they can be differentiated probabilistically and thereby demonstrate the high efficacy of primaquine treatment in preventing relapse.

    • Aimee R. Taylor
    • , James A. Watson
    •  & Nicholas J. White
  • Article
    | Open Access

    Structural variants may be omitted in sequence analysis despite their importance in genome variation and phenotypic impact. Here the authors present GraphTyper2, which uses pangenome graphs to genotype structural variants using short-reads and can be applied in large-scale sequencing studies.

    • Hannes P. Eggertsson
    • , Snaedis Kristmundsdottir
    •  & Pall Melsted
  • Article
    | Open Access

    Exceptional alpine plant diversity exists in the Hengduan Mountains. Here, through genome assembly and population genomics studies, the authors find notable intraspecific divergence among Cushion willow populations isolated by the sky island-like habitats and consider it contributes to speciation and biodiversity.

    • Jia-hui Chen
    • , Yuan Huang
    •  & Hang Sun
  • Article
    | Open Access

    Cucurbits fruits have diverse shapes and sizes, but their genomes evolution and genetic basis of diversity are unclear. Here, the authors show that the wax gourd genome has the most ancestral karyotype among cucurbits and identify candidate genes which contribute to large fruit size by comparative and population genomics analyses.

    • Dasen Xie
    • , Yuanchao Xu
    •  & Zhonghua Zhang
  • Article
    | Open Access

    The ‘parliament of genes’ hypothesis suggests that selfish genetic elements will be counteracted by suppressors that maintain equal transmission of the rest of the genome. Here, the authors find support for this hypothesis using mathematical models to explore a range of different scenarios.

    • Thomas W. Scott
    •  & Stuart A. West
  • Article
    | Open Access

    Various approaches are being used for polygenic prediction including Bayesian multiple regression methods that require access to individual-level genotype data. Here, the authors extend BayesR to utilise GWAS summary statistics (SBayesR) and show that it outperforms other summary statistic-based methods.

    • Luke R. Lloyd-Jones
    • , Jian Zeng
    •  & Peter M. Visscher
  • Article
    | Open Access

    Rare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals. Here, Oetjens et al. systematically study the contribution of common genetic variation to variable expressivity of RGDs and find it is frequently influenced by polygenic factors identified in genome-wide association studies of relevant traits.

    • M. T. Oetjens
    • , M. A. Kelly
    •  & D. H. Ledbetter
  • Article
    | Open Access

    Based on single worm whole genome sequencing, the authors here characterise the global evolution of the gastrointestinal parasite Haemonchus contortus and identify genes that play a role in drug resistance as well as climate-driven adaptations involving an epigenetic regulator.

    • G. Sallé
    • , S. R. Doyle
    •  & J. A. Cotton
  • Article
    | Open Access

    Date palm is an important fruit crop in the Middle East and North Africa. Here, the authors report an improved genome assembly of this species and perform GWAS mapping of sex determining region and 21 fruit traits using high density SNP data generated from re-sequencing of the mapping population.

    • Khaled M. Hazzouri
    • , Muriel Gros-Balthazard
    •  & Michael D. Purugganan
  • Article
    | Open Access

    Retrotransposition events have been linked to some human disorders. Here, Gardner et al. systematically search for mobile genetic elements (ME) in trio whole exome-sequencing datasets and ascertain 9 de novo MEs and further estimate genome-wide germline ME burden and constraint.

    • Eugene J. Gardner
    • , Elena Prigmore
    •  & Matthew E. Hurles
  • Article
    | Open Access

    Thousands of genetic loci are known to associate with human height, but these are mainly based on studies in European ancestry populations. Here, Akiyama et al. construct a genotype reference panel for the Japanese population followed by GWAS and report 573 height associated variants in 191,787 Japanese.

    • Masato Akiyama
    • , Kazuyoshi Ishigaki
    •  & Yoichiro Kamatani
  • Article
    | Open Access

    The majority of published GWAS was performed in European ancestry populations. Here, Kuchenbaecker et al., test to which extent lipid loci are shared and find that the major lipid loci are mostly transferrable between Europeans and Asians while there are notable exceptions for African populations.

    • Karoline Kuchenbaecker
    • , Nikita Telkar
    •  & Dieter Wolke
  • Article
    | Open Access

    Ecological speciation can proceed rapidly, but the origin of genetic variation facilitating it has remained elusive. Here, the authors show that secondary contact and introgression between deeply diverged lineages of stickleback fish facilitated rapid ecological speciation into lake and stream ecotypes in Lake Constance.

    • David A. Marques
    • , Kay Lucek
    •  & Ole Seehausen