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      Genome Sequence of the Lager Brewing Yeast, an Interspecies Hybrid

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          Abstract

          This work presents the genome sequencing of the lager brewing yeast ( Saccharomyces pastorianus) Weihenstephan 34/70, a strain widely used in lager beer brewing. The 25 Mb genome comprises two nuclear sub-genomes originating from Saccharomyces cerevisiae and Saccharomyces bayanus and one circular mitochondrial genome originating from S. bayanus. Thirty-six different types of chromosomes were found including eight chromosomes with translocations between the two sub-genomes, whose breakpoints are within the orthologous open reading frames. Several gene loci responsible for typical lager brewing yeast characteristics such as maltotriose uptake and sulfite production have been increased in number by chromosomal rearrangements. Despite an overall high degree of conservation of the synteny with S. cerevisiae and S. bayanus, the syntenies were not well conserved in the sub-telomeric regions that contain lager brewing yeast characteristic and specific genes. Deletion of larger chromosomal regions, a massive unilateral decrease of the ribosomal DNA cluster and bilateral truncations of over 60 genes reflect a post-hybridization evolution process. Truncations and deletions of less efficient maltose and maltotriose uptake genes may indicate the result of adaptation to brewing. The genome sequence of this interspecies hybrid yeast provides a new tool for better understanding of lager brewing yeast behavior in industrial beer production.

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          Sequencing and comparison of yeast species to identify genes and regulatory elements.

          Identifying the functional elements encoded in a genome is one of the principal challenges in modern biology. Comparative genomics should offer a powerful, general approach. Here, we present a comparative analysis of the yeast Saccharomyces cerevisiae based on high-quality draft sequences of three related species (S. paradoxus, S. mikatae and S. bayanus). We first aligned the genomes and characterized their evolution, defining the regions and mechanisms of change. We then developed methods for direct identification of genes and regulatory motifs. The gene analysis yielded a major revision to the yeast gene catalogue, affecting approximately 15% of all genes and reducing the total count by about 500 genes. The motif analysis automatically identified 72 genome-wide elements, including most known regulatory motifs and numerous new motifs. We inferred a putative function for most of these motifs, and provided insights into their combinatorial interactions. The results have implications for genome analysis of diverse organisms, including the human.
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            Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789.

            We sequenced the genome of Saccharomyces cerevisiae strain YJM789, which was derived from a yeast isolated from the lung of an AIDS patient with pneumonia. The strain is used for studies of fungal infections and quantitative genetics because of its extensive phenotypic differences to the laboratory reference strain, including growth at high temperature and deadly virulence in mouse models. Here we show that the approximately 12-Mb genome of YJM789 contains approximately 60,000 SNPs and approximately 6,000 indels with respect to the reference S288c genome, leading to protein polymorphisms with a few known cases of phenotypic changes. Several ORFs are found to be unique to YJM789, some of which might have been acquired through horizontal transfer. Localized regions of high polymorphism density are scattered over the genome, in some cases spanning multiple ORFs and in others concentrated within single genes. The sequence of YJM789 contains clues to pathogenicity and spurs the development of more powerful approaches to dissecting the genetic basis of complex hereditary traits.
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              Double-strand breaks associated with repetitive DNA can reshape the genome.

              Ionizing radiation is an established source of chromosome aberrations (CAs). Although double-strand breaks (DSBs) are implicated in radiation-induced and other CAs, the underlying mechanisms are poorly understood. Here, we show that, although the vast majority of randomly induced DSBs in G(2) diploid yeast cells are repaired efficiently through homologous recombination (HR) between sister chromatids or homologous chromosomes, approximately 2% of all DSBs give rise to CAs. Complete molecular analysis of the genome revealed that nearly all of the CAs resulted from HR between nonallelic repetitive elements, primarily Ty retrotransposons. Nonhomologous end-joining (NHEJ) accounted for few, if any, of the CAs. We conclude that only those DSBs that fall at the 3-5% of the genome composed of repetitive DNA elements are efficient at generating rearrangements with dispersed small repeats across the genome, whereas DSBs in unique sequences are confined to recombinational repair between the large regions of homology contained in sister chromatids or homologous chromosomes. Because repeat-associated DSBs can efficiently lead to CAs and reshape the genome, they could be a rich source of evolutionary change.
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                Author and article information

                Journal
                DNA Res
                dnares
                dnares
                DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
                Oxford University Press
                1340-2838
                1756-1663
                April 2009
                4 March 2009
                4 March 2009
                : 16
                : 2
                : 115-129
                Affiliations
                [1 ]R&D Planning Division, Suntory Limited , 1-1-1, Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan
                [2 ]Mitsubishi Research Institute, Advanced Science and Technology Group , 3-6 Otemachi 2-chome Chiyoda-ku, Tokyo 100-8141, Japan
                [3 ]Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo , Kashiwa-no-ha 5-1-5, Kashiwa, Chiba 277-8561, Japan
                [4 ]Florigene Pty, Ltd , 1 Park Drive, Bundoora, VIC 3083, Australia
                Author notes
                [†]

                Present address: AZTI-Tecnalia, Food Research Division, Parque Tecnológico de Bizkaia, Astondo Bidea 609, 48160, Derio, Spain

                [* ]To whom correspondence should be addressed. Tel. +81 75-962-2365. Fax. +81 75-962-3791. E-mail: yoshihiro_nakao@ 123456suntory.co.jp
                Article
                dsp003
                10.1093/dnares/dsp003
                2673734
                19261625
                a8075152-4ebd-4adf-826e-e39e503e0e14
                © The Author 2009. Kazusa DNA Research Institute.

                The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

                History
                : 30 September 2008
                : 7 February 2009
                Categories
                Full Papers

                Genetics
                genome,interspecies hybrid,beer,larger yeast,saccharomyces pastorianus
                Genetics
                genome, interspecies hybrid, beer, larger yeast, saccharomyces pastorianus

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