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AGAPE (Automated Genome Analysis PipelinE) for pan-genome analysis of Saccharomyces cerevisiae.

Song G, Dickins BJ, Demeter J, Engel S, Gallagher J, Choe K, Dunn B, Snyder M, Cherry JM - PLoS ONE (2015)

Bottom Line: To assign strain-specific functional annotations, we identified genes that were not present in the reference genome.The functional roles of novel genes not found in the reference genome and associated with strains or groups of strains appear to be consistent with anticipated adaptations in specific lineages.Our new tool set will enhance our understanding of genomic and functional evolution in S. cerevisiae, and will be available to the yeast genetics and molecular biology community.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.

ABSTRACT
The characterization and public release of genome sequences from thousands of organisms is expanding the scope for genetic variation studies. However, understanding the phenotypic consequences of genetic variation remains a challenge in eukaryotes due to the complexity of the genotype-phenotype map. One approach to this is the intensive study of model systems for which diverse sources of information can be accumulated and integrated. Saccharomyces cerevisiae is an extensively studied model organism, with well-known protein functions and thoroughly curated phenotype data. To develop and expand the available resources linking genomic variation with function in yeast, we aim to model the pan-genome of S. cerevisiae. To initiate the yeast pan-genome, we newly sequenced or re-sequenced the genomes of 25 strains that are commonly used in the yeast research community using advanced sequencing technology at high quality. We also developed a pipeline for automated pan-genome analysis, which integrates the steps of assembly, annotation, and variation calling. To assign strain-specific functional annotations, we identified genes that were not present in the reference genome. We classified these according to their presence or absence across strains and characterized each group of genes with known functional and phenotypic features. The functional roles of novel genes not found in the reference genome and associated with strains or groups of strains appear to be consistent with anticipated adaptations in specific lineages. As more S. cerevisiae strain genomes are released, our analysis can be used to collate genome data and relate it to lineage-specific patterns of genome evolution. Our new tool set will enhance our understanding of genomic and functional evolution in S. cerevisiae, and will be available to the yeast genetics and molecular biology community.

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Phylogenetic tree of the non-reference MAL gene family.The MAL23, MAL43, MAL63, and MAL64 genes are known non-reference features that may be associated with maltose activator function. We included all non-reference MAL activator genes identified in S. cerevisiae including sequences from this study, sequences from Bergstrom et al. [17], and ones deposited in the NCBI protein database. The MAL genes have been found in environmental and saké strains, but have not been detected in baking and European wine strains. One group of MAL genes in the upper part of the gene tree, detected in K11, YPS128, YPS163, UWOPS87, UWOPS83, SK1, and DBVPG6044 strains, is clustered separately from the other MAL genes.
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pone.0120671.g006: Phylogenetic tree of the non-reference MAL gene family.The MAL23, MAL43, MAL63, and MAL64 genes are known non-reference features that may be associated with maltose activator function. We included all non-reference MAL activator genes identified in S. cerevisiae including sequences from this study, sequences from Bergstrom et al. [17], and ones deposited in the NCBI protein database. The MAL genes have been found in environmental and saké strains, but have not been detected in baking and European wine strains. One group of MAL genes in the upper part of the gene tree, detected in K11, YPS128, YPS163, UWOPS87, UWOPS83, SK1, and DBVPG6044 strains, is clustered separately from the other MAL genes.

Mentions: At an intermediate stage of saké fermentation maltose is produced [54], potentially selecting for the retention, evolution, or horizontal acquisition of maltose utilization genes. Mutagenized strains of saké yeast with low maltose utilization appear to generate higher levels of malate [55], an organic acid contributing to the flavor of the beverage. Genes for maltose permease (GenBank BAB59002.1) and maltase (GenBank BAB59003.1) have been identified in Aspergillus oryzae and appear to be in a gene cluster with a regulatory gene [56]. Several maltose gene clusters are present in the S. cerevisiae pan-genome (Fig. 6). A maltose gene cluster such as MAL6 typically consists of a maltose permease (MAL61), maltase (MAL62), and a MAL regulatory/activator gene (MAL63). Constitutively active forms of the regulatory proteins coded for by these genes have also been identified and appear to relate to loss of function mutations affecting C-terminal residues responsible for negative regulatory function [57]. At the MAL6 locus an additional activator gene MAL64 has been described [58]. A premature termination codon in MAL64 confers constitutive expression [57] although the function of the wild-type allele is unclear.


AGAPE (Automated Genome Analysis PipelinE) for pan-genome analysis of Saccharomyces cerevisiae.

Song G, Dickins BJ, Demeter J, Engel S, Gallagher J, Choe K, Dunn B, Snyder M, Cherry JM - PLoS ONE (2015)

Phylogenetic tree of the non-reference MAL gene family.The MAL23, MAL43, MAL63, and MAL64 genes are known non-reference features that may be associated with maltose activator function. We included all non-reference MAL activator genes identified in S. cerevisiae including sequences from this study, sequences from Bergstrom et al. [17], and ones deposited in the NCBI protein database. The MAL genes have been found in environmental and saké strains, but have not been detected in baking and European wine strains. One group of MAL genes in the upper part of the gene tree, detected in K11, YPS128, YPS163, UWOPS87, UWOPS83, SK1, and DBVPG6044 strains, is clustered separately from the other MAL genes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363492&req=5

pone.0120671.g006: Phylogenetic tree of the non-reference MAL gene family.The MAL23, MAL43, MAL63, and MAL64 genes are known non-reference features that may be associated with maltose activator function. We included all non-reference MAL activator genes identified in S. cerevisiae including sequences from this study, sequences from Bergstrom et al. [17], and ones deposited in the NCBI protein database. The MAL genes have been found in environmental and saké strains, but have not been detected in baking and European wine strains. One group of MAL genes in the upper part of the gene tree, detected in K11, YPS128, YPS163, UWOPS87, UWOPS83, SK1, and DBVPG6044 strains, is clustered separately from the other MAL genes.
Mentions: At an intermediate stage of saké fermentation maltose is produced [54], potentially selecting for the retention, evolution, or horizontal acquisition of maltose utilization genes. Mutagenized strains of saké yeast with low maltose utilization appear to generate higher levels of malate [55], an organic acid contributing to the flavor of the beverage. Genes for maltose permease (GenBank BAB59002.1) and maltase (GenBank BAB59003.1) have been identified in Aspergillus oryzae and appear to be in a gene cluster with a regulatory gene [56]. Several maltose gene clusters are present in the S. cerevisiae pan-genome (Fig. 6). A maltose gene cluster such as MAL6 typically consists of a maltose permease (MAL61), maltase (MAL62), and a MAL regulatory/activator gene (MAL63). Constitutively active forms of the regulatory proteins coded for by these genes have also been identified and appear to relate to loss of function mutations affecting C-terminal residues responsible for negative regulatory function [57]. At the MAL6 locus an additional activator gene MAL64 has been described [58]. A premature termination codon in MAL64 confers constitutive expression [57] although the function of the wild-type allele is unclear.

Bottom Line: To assign strain-specific functional annotations, we identified genes that were not present in the reference genome.The functional roles of novel genes not found in the reference genome and associated with strains or groups of strains appear to be consistent with anticipated adaptations in specific lineages.Our new tool set will enhance our understanding of genomic and functional evolution in S. cerevisiae, and will be available to the yeast genetics and molecular biology community.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.

ABSTRACT
The characterization and public release of genome sequences from thousands of organisms is expanding the scope for genetic variation studies. However, understanding the phenotypic consequences of genetic variation remains a challenge in eukaryotes due to the complexity of the genotype-phenotype map. One approach to this is the intensive study of model systems for which diverse sources of information can be accumulated and integrated. Saccharomyces cerevisiae is an extensively studied model organism, with well-known protein functions and thoroughly curated phenotype data. To develop and expand the available resources linking genomic variation with function in yeast, we aim to model the pan-genome of S. cerevisiae. To initiate the yeast pan-genome, we newly sequenced or re-sequenced the genomes of 25 strains that are commonly used in the yeast research community using advanced sequencing technology at high quality. We also developed a pipeline for automated pan-genome analysis, which integrates the steps of assembly, annotation, and variation calling. To assign strain-specific functional annotations, we identified genes that were not present in the reference genome. We classified these according to their presence or absence across strains and characterized each group of genes with known functional and phenotypic features. The functional roles of novel genes not found in the reference genome and associated with strains or groups of strains appear to be consistent with anticipated adaptations in specific lineages. As more S. cerevisiae strain genomes are released, our analysis can be used to collate genome data and relate it to lineage-specific patterns of genome evolution. Our new tool set will enhance our understanding of genomic and functional evolution in S. cerevisiae, and will be available to the yeast genetics and molecular biology community.

Show MeSH
Related in: MedlinePlus