title: Low Base-Substitution Mutation Rate in the Germline Genome of the Ciliate Tetrahymena thermophil.
abstract: Mutation is the ultimate source of all genetic variation and is, therefore, central to evolutionary change. Previous work on Paramecium tetraurelia found an unusually low germline base-substitution mutation rate in this ciliate. Here, we tested the generality of this result among ciliates using Tetrahymena thermophila. We sequenced the genomes of 10 lines of T. thermophila that had each undergone approximately 1,000 generations of mutation accumulation (MA). We applied an existing mutation-calling pipeline and developed a new probabilistic mutation detection approach that directly models the design of an MA experiment and accommodates the noise introduced by mismapped reads. Our probabilistic mutation-calling method provides a straightforward way of estimating the number of sites at which a mutation could have been called if one was present, providing the denominator for our mutation rate calculations. From these methods, we find that T. thermophila has a germline base-substitution mutation rate of 7.61 × 10 - 12 per-site, per cell division, which is consistent with the low base-substitution mutation rate in P. tetraurelia. Over the course of the evolution experiment, genomic exclusion lines derived from the MA lines experienced a fitness decline that cannot be accounted for by germline base-substitution mutations alone, suggesting that other genetic or epigenetic factors must be involved. Because selection can only operate to reduce mutation rates based upon the "visible" mutational load, asexual reproduction with a transcriptionally silent germline may allow ciliates to evolve extremely low germline mutation rates.
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.|Department of Biology, Indiana University, Bloomington, IN, USA.
authors.forename: Hongan
authors.initials: H
authors.lastname: Long
authors.affiliation: The Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Winter
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Allan Y-C
authors.initials: AY
authors.lastname: Chang
authors.affiliation: Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA.
authors.forename: Way
authors.initials: W
authors.lastname: Sung
authors.affiliation: The Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Wu
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Mariel
authors.initials: M
authors.lastname: Balboa
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Ricardo B R
authors.initials: RBR
authors.lastname: Azevedo
authors.affiliation: The Biodesign Institute, Arizona State University, Tempe, AZ, USA.|School of Life Sciences, Arizona State University, Tempe, AZ, USA.
authors.forename: Reed A
authors.initials: RA
authors.lastname: Cartwright
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Zufall
mesh_terms: D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D018503:Genome, Protozoan / Q000235:genetics*; D018095:Germ-Line Mutation; D059645:Mutation Rate; D012641:Selection, Genetic / Q000235:genetics*; D016808:Tetrahymena thermophila / Q000235:genetics*
keywords: Oligohymenophorea; drift-barrier hypothesis; macronucleus; microbial eukaryote; micronucleus; mutation accumulation