The evolutionary genomics of sexual recombination

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

The puzzling predominance of sexual reproduction amongst animals has been repeatedly identified as one of the major outstanding questions in biology and has received an enormous amount of study. Meiotic recombination is one of the fundamental forces of evolution and plays a very significant role in both generating and mixing the genetic diversity present in sexual organisms. Recombination is also suggested to be instrumental in shaping the content of eukaryotic genomes.

Here we propose to study the role of breeding system and recombination in shaping the content and diversity of animal genomes using an exceptionally powerful natural system- the Root Knot Nematodes. We will, for the first time, be able to take a comparative genomic view of radically different reproductive modes in a phylogenetic design. Together these studies will give us a novel and powerful understanding of the role sexual reproduction plays in shaping genome content.

Planned Impact

The principal users of this work will be the academic community interested in evolutionary biology, genomics, nematology, reproduction and diversity. The immediate outputs from this grant will be basic scientific understanding concerning the nature of genome change. The enormous agricultural importance of these species will also ensure that the impact of this work, production of genetic markers and characterising genes associated with attack of their plant hosts, will have lasting impacts.

This project will be published in open-access peer reviewed journals wherever possible, to give scientists, applied researchers, and the public maximum access.

The genomics age, and the interaction of this new technology with basic biology and agriculture will additionally be highlighted to school children taking GCSE and A-level science courses (and their parents). This will be accomplished by extending the interactions we already have in place. These include tours of the DNA labs, practical sessions investigating DNA, discussions of the science relating to genome with school children of ages 13-17, and presentation of our work at open days at both universities.

We will develop a dynamic web presence including blog and news feeds, and also prepare promotional materials for dissemination to schools, colleges and fellow institutions.

Publications

10 25 50
 
Title The genome of Caenorhabditis elegans 
Description The work is the complete genome of C. elegans printed in hardbound volumes, with each chromosome occupying two volumes, 12 volumes in all. The covers of the volumes tesselate to form a picture of the nematode, and the spinse align to make a picture of the nematode. The mitochondrial genome is supplied as an "erratum sheet". 
Type Of Art Artwork 
Year Produced 2014 
Impact The work has been on long term loan and is permanently exhibited in the Summerhall Arts Complex, Edinburgh, as part of a permanent exhibition curated by ASCUS. 
 
Title Transmissions exhibition 
Description The Blaxter lab collaborated closely wth artists-in-residence (see http://www.ascus.org.uk/ciie-micro-residency-artists-announced/) in the Centre for immunity Infection and Evolution to inspire and be part of the final exhibition "Transmissions". Mark Blaxter appears in the film work produced by Anne Milne, and the work of the lab inspired Jo hodges and Robbie Coleman to produce a piece dedicated to the lab. 
Type Of Art Artwork 
Year Produced 2014 
Impact 'Transmissions' was showcased to the general public within a group exhibition 'Parallel Perspectives' in Summerhall as part of the Edinburgh International Science Festival 2015 art programme, How The Light Gets In . This exhibition of work susequently travelled LifeSpace, Dundee, returning to Edinburgh to showcase at the Tent Gallery, Edinburgh College of Art. 
URL http://www.ascus.org.uk/ciie-micro-residency-2/
 
Description The genome of Meloidofyne floridensis has need sequenced and assembled, and the data are being written up for publication.These data suggest a very complex pattern of hybrid speciation in Meloidogyne, which has significant implications for control and identification. We have sequenced the genomes of nineteen strains from five species of Meloidogyne, with additional data from a sixth.
Exploitation Route The finding that many species of plant parasite are hybrids will impact on control and treatment strategies.
Sectors Agriculture, Food and Drink,Environment

URL http://www.meloidogyne.org/
 
Description DNA sequence data are at the heart of the ongoing genomics revolution in biology.

Recent advances in technology have changed the landscape of what is possible. These 'next generation' sequencing technologies permit whole genome-scale, sequence-based assays at reasonable cost and high accuracy, even for organisms where no genome research has been carried out previously. Similarly, the massive throughput and adaptability of the new systems opens up possibilities of genome-scale assays in clinical and other medical research, screening large numbers of samples for changes underpinning diseases and traits of interest.

The GenePool is a next-generation genomics and bioinformatics facility based within the School of Biological Sciences, The University of Edinburgh. We offer collaborative access to our advanced DNA sequencing, genotyping and bioinformatics capabilities, using ABI 3730 Sanger, Illumina and Roche 454 technology platforms.

We work in the main with the Edinburgh academic community (Edinburgh University, associated research Institutes and others), MRC-funded biomedical researchers throughout Scotland, Scottish Universities Life Science Alliance (SULSA) researchers, and NERC-funded science (through the NERC Biomolecular Analysis Facility (NBAF)).
 
Title 2013 Computational infrastructure upgrades 
Description The facility now runs a secure, powerful computer cluster running SGE, with several hundred cores and 2 terabytes (Tb) of RAM. The University of Edinburgh's HECTOR supercomputer and the Edinburgh Compute and Data Facilities (ECDF), a parallel compute cluster with over 3000 cores and several Tb of RAM, provide additional infrastructure. We have an advanced data store (with many hundreds of Tb of capacity) based on highly resilient technology to assure availability and security of data. 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact The increase in the computational resources has increased our resilience and security, and allows the facility to take on ever larger projects. 
URL http://genomics.ed.ac.uk
 
Title Computational infrastructure upgrades 2016 
Description In 2016 we invested in upgrading the laboratory compute infrastructure to ~600 compute cores and ~150 Tb of raw data storage, by installing new high performance blades and converting the architecture to a virtualised cloud. 
Type Of Material Technology assay or reagent 
Year Produced 2016 
Provided To Others? Yes  
Impact Our group, and many others, have used the improved computattion to expedite the achievement of analytic research aims, and to attempt new analyses previously limited by computational load. 
 
Title Computing Infrastructure Upgrades 2018-19 
Description In 2018 we upgraded the Blaxter lab compute cluster to be a cloud-based system and added RAM and compute nodes to a total of 1024 nodes and just over 6 Tb RAM. There is also a 0.33 Pbyte disk farm 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? Yes  
Impact The compute cluster is now used by seven research groups in the School of Biological Sciences, funded by NERC, BBSRC, ERC and Wellcome Trust 
 
Title HiSeq2500 
Description The HiSeq2500 is a key next generation sequencing platform that we have installed and offer to a wide range of research teams throughout the UK. While our roster of instruments is changed to suit requirements, we have had up to 5 HiSeq2500 instruments in the facility. 
Type Of Material Technology assay or reagent 
Year Produced 2014 
Provided To Others? Yes  
Impact The HiSeq2500 has generated data that underpin more than 300 papers published to date. 
URL http://genomics.ed.ac.uk
 
Title HiSeq4000 
Description The HiSeq4000 is a key next generation sequencing platform that we have installed and offer to a wide range of research teams throughout the UK. While our roster of instruments is changed to suit requirements, we currently have one HiSeq4000 instrument in the facility. 
Type Of Material Technology assay or reagent 
Year Produced 2015 
Provided To Others? Yes  
Impact The HiSeq4000 offers cheap, high quality sequence data for genome sequencing and resequencing, RNASeq and many other applications. 
URL http://genomics.ed.ac.uk
 
Title HiSeqX 
Description The HiSeqX is a key next generation sequencing platform that we have installed and offer to a wide range of research teams throughout the UK. While our roster of instruments is changed to suit requirements, we currently have 6 HiSeqX instruments in the facility. 
Type Of Material Technology assay or reagent 
Year Produced 2015 
Provided To Others? Yes  
Impact The HiSeqX allows the facility to sequence human and other genomes at very low per-base costs, promoting genetical and genomic research across the RC spectrum. 
URL http://genomics.ed.ac.uk
 
Title NEMBASE4 
Description NEMBASE is a database analysing the transcriptomes of 67 different species of nematode, including many important parasites of humans, andimals and plants. Nematode parasites are of major importance in human health and agriculture, and free-living species deliver essential ecosystem services. The genomics revolution has resulted in the production of many small datasets of expressed sequence tags (ESTs) from a phylogenetically wide range of nematode species, but these are not easily compared. NEMBASE4 presents a single portal onto extensively functionally annotated transcriptomes from over sixty species of nematodes, including plant and animal parasites and free-living taxa. Using the PartiGene suite of tools, we have assembled the ESTs publicly available for each species into a high-quality set of putative transcripts. These transcripts have been translated to produce a protein sequence resource, and each annotated with functional information derived from comparison to well-studied nematode species such as Caenorhabditis elegans and also other non-nematode resources. By cross-comparing the sequences within NEMBASE4, we have also generated a protein family assignment for each translation. The data are presented in an openly-accessible, interactive database. We have used NEMBASE4 to examine the uniqueness of the transcriptomes of major clades of parasitic nematodes, identifying lineage-restricted genes that may underpin particular parasitic phenotypes, and identify nematode-unique protein families that may be developed as drug targets. 
Type Of Material Database/Collection of data 
Year Produced 2010 
Provided To Others? Yes  
Impact NEMBASE gene models and analyses are exported widely to other analysis groups including WORMBASE and Nematode.net 
URL http://www.nematodes.org/nembase4/
 
Title nematod.es 
Description nematod.es is a collection housing nematode genome data in a set of BADGER genome exploration environments. 
Type Of Material Database/Collection of data 
Year Produced 2013 
Provided To Others? Yes  
Impact The database has been accessed thousands of times, largely for browsing and data download. The existence of the database has allowed us to build many fruitful collaborations. 
URL http://www.nematod.es
 
Title EasyMirror/EasyImport 
Description These tools simplify the rool out of customised ENSEMBL databases. 
Type Of Technology Software 
Year Produced 2016 
Open Source License? Yes  
Impact We have been inundated with requests for support and assistance in delivering these tools, and with praise for their ease of use and timeliness. 
URL http://www.genomehubs.org
 
Title TAGC-plots and Blobsplorer tools for genomics 
Description Generating the raw data for a de novo genome assembly project for a target eukaryotic species is relatively easy. This democratisation of access to large-scale data has allowed many research teams to plan to assemble the genomes of non-model organisms. These new genome targets are very different from the traditional, inbred, laboratory reared model organisms. They are often small, and cannot be isolated free of their environment - whether ingested food, the surrounding host organism of parasites, or commensal and symbiotic organisms attached to or within the individuals sampled. Preparation of pure DNA originating from a single species can be technically impossible, but assembly of mixed-organism DNA can be difficult, as most genome assemblers perform poorly when faced with multiple genomes in different stoichiometries. This class of problem is common in metagenomic datasets that deliberately try to capture all the genomes present in an environment, but replicon assembly is not often the goal of such programmes. Here we present an approach to extracting from mixed DNA sequence data subsets that correspond to single species' genomes and thus improving genome assembly. We use both numerical (proportion of GC bases and read coverage) and biological (best-matching sequence in annotated databases) indicators to aid partitioning of draft assembly contigs, and the reads that contribute to those contigs, into distinct bins that can then be subjected to rigorous, optimised assembly. We also present a tool, blobsplorer, that aids exploration and selection of subsets from GC/coverage/taxonomy annotated datasets. Partitioning the data in this way "rescues" poorly assembled genomes, and reveals unexpected symbionts and commensals in eukaryotic genome projects. The TAGC-plot pipeline script is available from http://github.com/blaxterlab/blobology, and the Blobsplorer tool from https://github.com/mojones/blobsplorer. 
Type Of Technology Software 
Year Produced 2013 
Open Source License? Yes  
Impact Blobsplorer/TAGC plots are now in wide use in genomics. The toolkit has been featured in several courses and publications. 
URL http://github.com/blaxterlab/blobology
 
Description Blaxter group - presentations and outreach 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Blaxter group presented work at a wide range of national and international conferences, including PopGroup, the Arthropod Genomics Workshop, The C. elegans International Meeting, The Hydra Helminthology meeting, The European Society for Nematology, The UK Genome Science meeting, and others. At many of these venues, in addition to offering platform or poster presentations, we also presented workshops or training activities.
Year(s) Of Engagement Activity 2016
 
Description Blaxter group presentations and outreach 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Mark Blaxter and research team communication and outreach 2015

Globodera genomics and blobtools software
25/02/2015 JHI Postgraduate Student Competition 2015 James Hutton Institute, Aberdeen, UK A tale of Two Peaks: Analysing Genomic Data from Potato Cyst Nematodes Talk
26/03/2015 JHI Cell and Molecular Sciences (CMS) seminar James Hutton Institute, Invergowrie, Dundee, UK Frustration and happiness : (De)-constructing parasite genomes Talk
16/06/2015 JHI Dundee effector consortium (DEC) meeting 2015 Birnam Arts and Conference Centre, Birnam, UK Variation within the Globodera pallida species complex: preliminary results Talk
03/09/2015 Molecular and Cellular Biology of Helminth Parasites IX Bratsera Hotel, Hydra, Greece Inter- and intra-specific analyses of the effector complement in potato cyst nematodes Poster
18/09/2015 UoE Postgraduate Poster Day University of Edinburgh, Edinburgh, UK Inter- and intra-specific analyses of the effector complement in potato cyst nematodes Poster
26/09/2015 Edinburgh University Doors Open Day University of Edinburgh, Edinburgh, UK Potato Cyst Nematodes (PCN) - Nematode parasites of potatoes Poster
30/11/2015 NextGenBug University of Edinburgh, Edinburgh, UK Blobtools: Blobology 2.0 Talk
01/12/2015 UK pollinator genomics meeting Roslin Institute, Edinburgh, UK Bees and Blobs Talk

LepBase
06/03/2015 EMARES Cambridge, UK The Bicyclus Genome Project Talk
06/03/2015 EMARES Cambridge, UK An introduction to Lepbase Talk
17/06/2015 Arthropod Genomics Manhattan, Kansas, USA Lepbase - A multi genome database for the Lepidoptera Poster
24/07/2015 10th Heliconius Meeting Gamboa, Panama Lepbase - A multi genome database for the Lepidoptera (API demonstration) Workshop
24/07/2015 10th Heliconius Meeting Panama Lepbase - A multi genome database for the Lepidoptera Poster
26/07/2015 10th Heliconius Meeting Panama Lepbase Workshop Talk
04/09/2015 Edinburgh Bioinformatics Edinburgh, UK Lepbase - A multi genome database for the Lepidoptera Talk
26/09/2015 Open Doors Day "Make a butterfly" interactive exhibition
26/09/2015 Edinburgh University Doors Open Day Edinburgh, UK Lepbase Multiple Sequence Alignments game Poster+Game
28/10/2015 NextgenBUG Dundee, UK Lepbase - an Ensembl (and more) for the Lepidoptera Talk

Nematode genomics
24.06.2015 20th International C. elegans Meeting Los Angeles USA A new evolutionary framework for the phylum Nematoda: a case study of HOX cluster evolution Poster
24.06.2015 20th International C. elegans Meeting Los Angeles USA Caenorhabditis Genomes Project Workshop (organiser and chair) Talk
24.06.2015 20th International C. elegans Meeting Los Angeles USA Current status of the CGP in Edinburgh Talk

Meloidogyne genomics
10-14 August 2015 ESEB Lausanne-Switzerland Genomic consequences of hybridization and the loss of meiotic recombination in Root-knot nematodes poster
15-18 December 2015 PopGroup Edinburgh-UK Genomic consequences of hybridization and the loss of meiotic recombination in Root-knot nematodes talk
23 February 2016 NextGenBug Edinburgh-UK Genomics of Root-knot nematodes talk
Year(s) Of Engagement Activity 2015
 
Description Blaxter lab workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Blaxter lab took our software products and research tools to various venues (Arthropod Genomics, UK Genome Science meeting, Butterfly Genomics) to present as workshops, training events or interactive sessions
Year(s) Of Engagement Activity 2016
 
Description Press releases and website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact We have engaged actively with the University press office to promote press coverage of our research outcomes, particularly major publications (which have had coverage in national and international newspapers) and in blogs and other online media. We have also promoted major new initiatives such as additional core funding of the Edinburgh genomics facility.

Increased visibility of Edinburgh Genomics within the community; requests for comment by funders and government on matters pertaining to genomics.
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013,2014,2015,2016