9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      The genome-wide rate and spectrum of spontaneous mutations differ between haploid and diploid yeast

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p id="d1899150e168">Organisms vary in the number of genome copies per cell: ploidy. By altering how DNA is replicated and repaired, ploidy may determine the number and types of mutations that arise, affecting how evolution proceeds. We sequenced the genomes of &gt;200 replicate lines of yeast ( <i>Saccharomyces cerevisiae</i>) with one versus two genome copies (haploid versus diploid) after accumulation of thousands of new mutations. Haploids were more susceptible to single-nucleotide mutations, particularly for DNA replicated later in the cell cycle, whereas large changes to genome structure were more common in diploids. Haploid and diploid populations will therefore have access to distinct kinds of genetic variation, contributing to differences in their evolutionary potential. </p><p class="first" id="d1899150e174">By altering the dynamics of DNA replication and repair, alternative ploidy states may experience different rates and types of new mutations, leading to divergent evolutionary outcomes. We report a direct comparison of the genome-wide spectrum of spontaneous mutations arising in haploids and diploids following a mutation-accumulation experiment in the budding yeast <i>Saccharomyces cerevisiae</i>. Characterizing the number, types, locations, and effects of thousands of mutations revealed that haploids were more prone to single-nucleotide mutations (SNMs) and mitochondrial mutations, while larger structural changes were more common in diploids. Mutations were more likely to be detrimental in diploids, even after accounting for the large impact of structural changes, contrary to the prediction that mutations would have weaker effects, due to masking, in diploids. Haploidy is expected to reduce the opportunity for conservative DNA repair involving homologous chromosomes, increasing the insertion-deletion rate, but we found little support for this idea. Instead, haploids were more susceptible to SNMs in late-replicating genomic regions, resulting in a ploidy difference in the spectrum of substitutions. In diploids, we detect mutation rate variation among chromosomes in association with centromere location, a finding that is supported by published polymorphism data. Diploids are not simply doubled haploids; instead, our results predict that the spectrum of spontaneous mutations will substantially shape the dynamics of genome evolution in haploid and diploid populations. </p>

          Related collections

          Most cited references48

          • Record: found
          • Abstract: found
          • Article: not found

          Effects of aneuploidy on cellular physiology and cell division in haploid yeast.

          Aneuploidy is a condition frequently found in tumor cells, but its effect on cellular physiology is not known. We have characterized one aspect of aneuploidy: the gain of extra chromosomes. We created a collection of haploid yeast strains that each bear an extra copy of one or more of almost all of the yeast chromosomes. Their characterization revealed that aneuploid strains share a number of phenotypes, including defects in cell cycle progression, increased glucose uptake, and increased sensitivity to conditions interfering with protein synthesis and protein folding. These phenotypes were observed only in strains carrying additional yeast genes, which indicates that they reflect the consequences of additional protein production as well as the resulting imbalances in cellular protein composition. We conclude that aneuploidy causes not only a proliferative disadvantage but also a set of phenotypes that is independent of the identity of the individual extra chromosomes.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A genome-wide view of the spectrum of spontaneous mutations in yeast.

            The mutation process ultimately defines the genetic features of all populations and, hence, has a bearing on a wide range of issues involving evolutionary genetics, inheritance, and genetic disorders, including the predisposition to cancer. Nevertheless, formidable technical barriers have constrained our understanding of the rate at which mutations arise and the molecular spectrum of their effects. Here, we report on the use of complete-genome sequencing in the characterization of spontaneously arising mutations in the yeast Saccharomyces cerevisiae. Our results confirm some findings previously obtained by indirect methods but also yield numerous unexpected findings, in particular a very high rate of point mutation and skewed distribution of base-substitution types in the mitochondrion, a very high rate of segmental duplication and deletion in the nuclear genome, and substantial deviations in the mutational profile among various model organisms.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast.

              Mass spectrometry is a powerful technology for the analysis of large numbers of endogenous proteins. However, the analytical challenges associated with comprehensive identification and relative quantification of cellular proteomes have so far appeared to be insurmountable. Here, using advances in computational proteomics, instrument performance and sample preparation strategies, we compare protein levels of essentially all endogenous proteins in haploid yeast cells to their diploid counterparts. Our analysis spans more than four orders of magnitude in protein abundance with no discrimination against membrane or low level regulatory proteins. Stable-isotope labelling by amino acids in cell culture (SILAC) quantification was very accurate across the proteome, as demonstrated by one-to-one ratios of most yeast proteins. Key members of the pheromone pathway were specific to haploid yeast but others were unaltered, suggesting an efficient control mechanism of the mating response. Several retrotransposon-associated proteins were specific to haploid yeast. Gene ontology analysis pinpointed a significant change for cell wall components in agreement with geometrical considerations: diploid cells have twice the volume but not twice the surface area of haploid cells. Transcriptome levels agreed poorly with proteome changes overall. However, after filtering out low confidence microarray measurements, messenger RNA changes and SILAC ratios correlated very well for pheromone pathway components. Systems-wide, precise quantification directly at the protein level opens up new perspectives in post-genomics and systems biology.
                Bookmark

                Author and article information

                Journal
                Proceedings of the National Academy of Sciences
                Proc Natl Acad Sci USA
                Proceedings of the National Academy of Sciences
                0027-8424
                1091-6490
                May 29 2018
                May 29 2018
                May 29 2018
                May 14 2018
                : 115
                : 22
                : E5046-E5055
                Article
                10.1073/pnas.1801040115
                5984525
                29760081
                684082e3-3cfc-4ca6-a919-2b63ce4c8370
                © 2018

                Free to read

                http://www.pnas.org/site/misc/userlicense.xhtml

                History

                Comments

                Comment on this article