title: Remarkably Divergent Regions Punctuate the Genome Assembly of the Caenorhabditis elegans Hawaiian Strain CB4856.
abstract: The Hawaiian strain (CB4856) of Caenorhabditis elegans is one of the most divergent from the canonical laboratory strain N2 and has been widely used in developmental, population, and evolutionary studies. To enhance the utility of the strain, we have generated a draft sequence of the CB4856 genome, exploiting a variety of resources and strategies. When compared against the N2 reference, the CB4856 genome has 327,050 single nucleotide variants (SNVs) and 79,529 insertion-deletion events that result in a total of 3.3 Mb of N2 sequence missing from CB4856 and 1.4 Mb of sequence present in CB4856 but not present in N2. As previously reported, the density of SNVs varies along the chromosomes, with the arms of chromosomes showing greater average variation than the centers. In addition, we find 61 regions totaling 2.8 Mb, distributed across all six chromosomes, which have a greatly elevated SNV density, ranging from 2 to 16% SNVs. A survey of other wild isolates show that the two alternative haplotypes for each region are widely distributed, suggesting they have been maintained by balancing selection over long evolutionary times. These divergent regions contain an abundance of genes from large rapidly evolving families encoding F-box, MATH, BATH, seven-transmembrane G-coupled receptors, and nuclear hormone receptors, suggesting that they provide selective advantages in natural environments. The draft sequence makes available a comprehensive catalog of sequence differences between the CB4856 and N2 strains that will facilitate the molecular dissection of their phenotypic differences. Our work also emphasizes the importance of going beyond simple alignment of reads to a reference genome when assessing differences between genomes.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195.
authors.forename: Owen A
authors.initials: OA
authors.lastname: Thompson
authors.affiliation: Laboratory of Nematology, Wageningen University, 6708 PB Wageningen, The Netherlands.
authors.forename: L Basten
authors.initials: LB
authors.lastname: Snoek
authors.affiliation: Laboratory of Bioinformatics, Wageningen University, NL-6708 PB Wageningen, The Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: Nijveen
authors.affiliation: Laboratory of Nematology, Wageningen University, 6708 PB Wageningen, The Netherlands.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Sterken
authors.affiliation: Laboratory of Nematology, Wageningen University, 6708 PB Wageningen, The Netherlands.
authors.forename: Rita J M
authors.initials: RJ
authors.lastname: Volkers
authors.affiliation: Centre for Genome Research, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Brenchley
authors.affiliation: Centre for Genome Research, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
authors.forename: Arjen
authors.initials: A
authors.lastname: Van't Hof
authors.affiliation: Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Roel P J
authors.initials: RP
authors.lastname: Bevers
authors.affiliation: Centre for Genome Research, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Cossins
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel 32000.
authors.forename: Itai
authors.initials: I
authors.lastname: Yanai
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Alex
authors.initials: A
authors.lastname: Hajnal
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmid
authors.affiliation: Department of Zoology and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Jaryn D
authors.initials: JD
authors.lastname: Perkins
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195.
authors.forename: David
authors.initials: D
authors.lastname: Spencer
authors.affiliation: Howard Hughes Medical Institute, Department of Human Genetics and Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, California 90095.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kruglyak
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Andersen
authors.affiliation: Department of Zoology and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Moerman
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195.
authors.forename: LaDeana W
authors.initials: LW
authors.lastname: Hillier
authors.affiliation: Laboratory of Nematology, Wageningen University, 6708 PB Wageningen, The Netherlands.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Kammenga
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195 watersto@u.washington.edu.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Waterston
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D014644:Genetic Variation; D049751:Genome, Helminth; D023281:Genomics; D054643:INDEL Mutation; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide
keywords: C. elegans; evolution; genome assembly; variation