title: An improved genome assembly uncovers prolific tandem repeats in Atlantic cod.
abstract: The first Atlantic cod (Gadus morhua) genome assembly published in 2011 was one of the early genome assemblies exclusively based on high-throughput 454 pyrosequencing. Since then, rapid advances in sequencing technologies have led to a multitude of assemblies generated for complex genomes, although many of these are of a fragmented nature with a significant fraction of bases in gaps. The development of long-read sequencing and improved software now enable the generation of more contiguous genome assemblies.
  
  
  
  By combining data from Illumina, 454 and the longer PacBio sequencing technologies, as well as integrating the results of multiple assembly programs, we have created a substantially improved version of the Atlantic cod genome assembly. The sequence contiguity of this assembly is increased fifty-fold and the proportion of gap-bases has been reduced fifteen-fold. Compared to other vertebrates, the assembly contains an unusual high density of tandem repeats (TRs). Indeed, retrospective analyses reveal that gaps in the first genome assembly were largely associated with these TRs. We show that 21% of the TRs across the assembly, 19% in the promoter regions and 12% in the coding sequences are heterozygous in the sequenced individual.
  
  
  
  The inclusion of PacBio reads combined with the use of multiple assembly programs drastically improved the Atlantic cod genome assembly by successfully resolving long TRs. The high frequency of heterozygous TRs within or in the vicinity of genes in the genome indicate a considerable standing genomic variation in Atlantic cod populations, which is likely of evolutionary importance.
authors.affiliation: Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, NO-0316, Norway. o.k.torresen@ibv.uio.no.
authors.forename: Ole K
authors.initials: OK
authors.lastname: Tørresen
authors.affiliation: Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, NO-0316, Norway.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Star
authors.affiliation: Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, NO-0316, Norway.|Department of Natural Sciences, University of Agder, Kristiansand, NO-4604, Norway.
authors.forename: Sissel
authors.initials: S
authors.lastname: Jentoft
authors.affiliation: Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, NO-0316, Norway.
authors.forename: William B
authors.initials: WB
authors.lastname: Reinar
authors.affiliation: Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, Ås, NO-1432, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Grove
authors.affiliation: J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, 20850, MD, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Miller
authors.affiliation: Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, MD, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Walenz
authors.affiliation: Yale School of Medicine, Yale University, New Haven, 06520, CT, USA.
authors.forename: James
authors.initials: J
authors.lastname: Knight
authors.affiliation: Pacific Biosciences, Menlo Park CA, USA.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Ekholm
authors.affiliation: Pacific Biosciences, Menlo Park CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Peluso
authors.affiliation: Institute of Marine Research, Nordnes, Bergen, NO-5817, Norway.
authors.forename: Rolf B
authors.initials: RB
authors.lastname: Edvardsen
authors.affiliation: Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, NO-0316, Norway.
authors.forename: Ave
authors.initials: A
authors.lastname: Tooming-Klunderud
authors.affiliation: Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, NO-0316, Norway.
authors.forename: Morten
authors.initials: M
authors.lastname: Skage
authors.affiliation: Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, Ås, NO-1432, Norway.
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Lien
authors.affiliation: Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, NO-0316, Norway.
authors.forename: Kjetill S
authors.initials: KS
authors.lastname: Jakobsen
authors.affiliation: Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, NO-0316, Norway. lex.nederbragt@ibv.uio.no.|Biomedical Informatics Research Group, Department of Informatics, University of Oslo, Oslo, NO-0316, Norway. lex.nederbragt@ibv.uio.no.
authors.forename: Alexander J
authors.identifier: 0000-0001-5539-0999
authors.initials: AJ
authors.lastname: Nederbragt
mesh_terms: D000818:Animals; D048389:Gadus morhua / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D006579:Heterozygote; D058977:Molecular Sequence Annotation; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences / Q000235:genetics*
keywords: Assembly algorithms; Assembly consolidation; Dinucleotide repeats; Gadus morhua; Heterozygosity; Indel polymorphism; Long-read sequencing technology; Microsatellites; PacBio; Repetitive DNA