The Spontaneous Mutation Rate in the Fission Yeast Schizosaccharomyces pombe

The rate at which new mutations arise in the genome is a key factor in the evolution and adaptation of species. Here we describe the rate and spectrum of spontaneous mutations for the fission yeast Schizosaccharomyces pombe, a key model organism with many similarities to higher eukaryotes. We undertook an ∼1700-generation mutation accumulation (MA) experiment with a haploid S. pombe, generating 422 single-base substitutions and 119 insertion-deletion mutations (indels) across the 96 replicates. This equates to a base-substitution mutation rate of 2.00 × 10−10 mutations per site per generation, similar to that reported for the distantly related budding yeast Saccharomyces cerevisiae. However, these two yeast species differ dramatically in their spectrum of base substitutions, the types of indels (S. pombe is more prone to insertions), and the pattern of selection required to counteract a strong AT-biased mutation rate. Overall, our results indicate that GC-biased gene conversion does not play a major role in shaping the nucleotide composition of the S. pombe genome and suggest that the mechanisms of DNA maintenance may have diverged significantly between fission and budding yeasts. Unexpectedly, CpG sites appear to be excessively liable to mutation in both species despite the likely absence of DNA methylation.

[1]  Leonid Kruglyak,et al.  Comprehensive polymorphism survey elucidates population structure of Saccharomyces cerevisiae , 2009, Nature.

[2]  Erik Kaestner,et al.  The Origins Of Genome Architecture , 2016 .

[3]  M. Lynch.  Rate, molecular spectrum, and consequences of human mutation , 2010, Proceedings of the National Academy of Sciences.

[4]  A. Jeltsch,et al.  Pmt1, a Dnmt2 homolog in Schizosaccharomyces pombe, mediates tRNA methylation in response to nutrient signaling , 2012, Nucleic acids research.

[5]  Edison T. Liu,et al.  Global Profiling of DNA Replication Timing and Efficiency Reveals that Efficient Replication/Firing Occurs Late during S-Phase in S. pombe , 2007, PloS one.

[6]  Richard M. Clark,et al.  The Rate and Molecular Spectrum of Spontaneous Mutations in Arabidopsis thaliana , 2010, Science.

[7]  H. Blom,et al.  Cytosine DNA Methylation Is Found in Drosophila melanogaster but Absent in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Other Yeast Species , 2014, Analytical chemistry.

[8]  S. Pratt,et al.  Population genomic analysis of outcrossing and recombination in yeast , 2006, Nature Genetics.

[9]  G. Chua,et al.  Deciphering the Transcriptional-Regulatory Network of Flocculation in Schizosaccharomyces pombe , 2012, PLoS genetics.

[10]  A. Burt,et al.  Population genomics of the wild yeast Saccharomyces paradoxus: Quantifying the life cycle , 2008, Proceedings of the National Academy of Sciences.

[11]  M. Lynch,et al.  Background Mutational Features of the Radiation-Resistant Bacterium Deinococcus radiodurans. , 2015, Molecular biology and evolution.

[12]  Bifeng Yuan,et al.  Widespread existence of cytosine methylation in yeast DNA measured by gas chromatography/mass spectrometry. , 2012, Analytical chemistry.

[13]  Peter C. Dolan,et al.  Variation in Base-Substitution Mutation in Experimental and Natural Lineages of Caenorhabditis Nematodes , 2012, Genome biology and evolution.

[14]  Broome,et al.  Literature cited , 1924, A Guide to the Carnivores of Central America.

[15]  Abraham E. Tucker,et al.  Extraordinary genome stability in the ciliate Paramecium tetraurelia , 2012, Proceedings of the National Academy of Sciences.

[16]  Marian Thomson,et al.  Analysis of the genome sequences of three Drosophila melanogaster spontaneous mutation accumulation lines. , 2009, Genome research.

[17]  W. Ewens.  Genetics and analysis of quantitative traits , 1999 .

[18]  D. Petrov,et al.  Evidence That Mutation Is Universally Biased towards AT in Bacteria , 2010, PLoS genetics.

[19]  W. J. Dickinson,et al.  A genome-wide view of the spectrum of spontaneous mutations in yeast , 2008, Proceedings of the National Academy of Sciences.

[20]  D. Halligan,et al.  Estimation of the Spontaneous Mutation Rate per Nucleotide Site in a Drosophila melanogaster Full-Sib Family , 2013, Genetics.

[21]  Robert P. Davey,et al.  Population genomics of domestic and wild yeasts , 2008, Nature.

[22]  Brendan D. O'Fallon,et al.  The genomic and phenotypic diversity of Schizosaccharomyces pombe , 2015, Nature Genetics.

[23]  K. Takegawa,et al.  Identification of a galactose‐specific flocculin essential for non‐sexual flocculation and filamentous growth in Schizosaccharomyces pombe , 2011, Molecular microbiology.

[24]  R. Wilson,et al.  BreakDancer: An algorithm for high resolution mapping of genomic structural variation , 2009, Nature Methods.

[25]  K. Ohta,et al.  Population Genomics of the Fission Yeast Schizosaccharomyces pombe , 2014, PloS one.

[26]  Manolis Kellis,et al.  Comparative Functional Genomics of the Fission Yeasts , 2011, Science.

[27]  Daniel R. Schrider,et al.  Rates and Genomic Consequences of Spontaneous Mutational Events in Drosophila melanogaster , 2013, Genetics.

[28]  V. Wood,et al.  Retrotransposons and their recognition of pol II promoters: a comprehensive survey of the transposable elements from the complete genome sequence of Schizosaccharomyces pombe. , 2003, Genome research.

[29]  N. Colegrave,et al.  Estimate of the Spontaneous Mutation Rate in Chlamydomonas reinhardtii , 2012, Genetics.

[30]  P. Baumann,et al.  A Geographically Diverse Collection of Schizosaccharomyces pombe Isolates Shows Limited Phenotypic Variation but Extensive Karyotypic Diversity , 2011, G3: Genes | Genomes | Genetics.

[31]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[32]  R. Aebersold,et al.  Quantitative Analysis of Fission Yeast Transcriptomes and Proteomes in Proliferating and Quiescent Cells , 2012, Cell.

[33]  M. Lynch,et al.  Asymmetric Context-Dependent Mutation Patterns Revealed through Mutation-Accumulation Experiments. , 2015, Molecular biology and evolution.

[34]  P. Keightley,et al.  Estimation of the Spontaneous Mutation Rate in Heliconius melpomene , 2014, Molecular biology and evolution.

[35]  Adam Frost,et al.  Functional Repurposing Revealed by Comparing S. pombe and S. cerevisiae Genetic Interactions , 2012, Cell.

[36]  Kai Ye,et al.  Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads , 2009, Bioinform..

[37]  David W. Hall,et al.  Precise estimates of mutation rate and spectrum in yeast , 2014, Proceedings of the National Academy of Sciences.

[38]  Karsten M. Borgwardt,et al.  Century-scale Methylome Stability in a Recently Diverged Arabidopsis thaliana Lineage , 2014, bioRxiv.

[39]  Thomas G. Doak,et al.  Drift-barrier hypothesis and mutation-rate evolution , 2012, Proceedings of the National Academy of Sciences.