title: High mutational rates of large-scale duplication and deletion in Daphnia pulex.
abstract: Knowledge of the genome-wide rate and spectrum of mutations is necessary to understand the origin of disease and the genetic variation driving all evolutionary processes. Here, we provide a genome-wide analysis of the rate and spectrum of mutations obtained in two Daphnia pulex genotypes via separate mutation-accumulation (MA) experiments. Unlike most MA studies that utilize haploid, homozygous, or self-fertilizing lines, D. pulex can be propagated ameiotically while maintaining a naturally heterozygous, diploid genome, allowing the capture of the full spectrum of genomic changes that arise in a heterozygous state. While base-substitution mutation rates are similar to those in other multicellular eukaryotes (about 4 × 10(-9) per site per generation), we find that the rates of large-scale (>100 kb) de novo copy-number variants (CNVs) are significantly elevated relative to those seen in previous MA studies. The heterozygosity maintained in this experiment allowed for estimates of gene-conversion processes. While most of the conversion tract lengths we report are similar to those generated by meiotic processes, we also find larger tract lengths that are indicative of mitotic processes. Comparison of MA lines to natural isolates reveals that a majority of large-scale CNVs in natural populations are removed by purifying selection. The mutations observed here share similarities with disease-causing, complex, large-scale CNVs, thereby demonstrating that MA studies in D. pulex serve as a system for studying the processes leading to such alterations.
authors.affiliation: School of Public and Environmental Affairs, Indiana University, Bloomington, Indiana 47405, USA;
authors.forename: Nathan
authors.initials: N
authors.lastname: Keith
authors.affiliation: Biology Department, Southern Arkansas University, Magnolia, Arkansas 71753, USA;
authors.forename: Abraham E
authors.initials: AE
authors.lastname: Tucker
authors.affiliation: School of Public and Environmental Affairs, Indiana University, Bloomington, Indiana 47405, USA;
authors.forename: Craig E
authors.initials: CE
authors.lastname: Jackson
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana 47405, USA;
authors.forename: Way
authors.initials: W
authors.lastname: Sung
authors.affiliation: Leibniz Institute of Freshwater Ecology and Inland Fisheries, Stechlin, 16775 Germany;
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Lucas Lledó
authors.affiliation: Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA;
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Schrider
authors.affiliation: Biology Department, Reed College, Portland, Oregon 97202, USA;
authors.forename: Sarah
authors.initials: S
authors.lastname: Schaack
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208, USA;
authors.forename: Jeffry L
authors.initials: JL
authors.lastname: Dudycha
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana 47405, USA;
authors.forename: Matthew
authors.initials: M
authors.lastname: Ackerman
authors.affiliation: School of Informatics and Computing, Indiana University, Bloomington, Indiana 47405, USA;
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Younge
authors.affiliation: School of Public and Environmental Affairs, Indiana University, Bloomington, Indiana 47405, USA; School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Shaw
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana 47405, USA;
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
mesh_terms: D000818:Animals; D056915:DNA Copy Number Variations; D003621:Daphnia / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D056726:Genetic Association Studies; D014644:Genetic Variation; D006579:Heterozygote; D008297:Male; D059645:Mutation Rate; D017422:Sequence Analysis, DNA