RT Journal A1 Andersen, Mikael R. A1 Salazar, Margarita P. A1 Schaap, Peter J. A1 van de Vondervoort, Peter J.I. A1 Culley, David A1 Thykaer, Jette A1 Frisvad, Jens C. A1 Nielsen, Kristian F. A1 Albang, Richard A1 Albermann, Kaj A1 Berka, Randy M. A1 Braus, Gerhard H. A1 Braus-Stromeyer, Susanna A. A1 Corrochano, Luis M. A1 Dai, Ziyu A1 van Dijck, Piet W.M. A1 Hofmann, Gerald A1 Lasure, Linda L. A1 Magnuson, Jon K. A1 Menke, Hildegard A1 Meijer, Martin A1 Meijer, Susan L. A1 Nielsen, Jakob B. A1 Nielsen, Michael L. A1 van Ooyen, Albert J.J. A1 Pel, Herman J. A1 Poulsen, Lars A1 Samson, Rob A. A1 Stam, Hein A1 Tsang, Adrian A1 van den Brink, Johannes M. A1 Atkins, Alex A1 Aerts, Andrea A1 Shapiro, Harris A1 Pangilinan, Jasmyn A1 Salamov, Asaf A1 Lou, Yigong A1 Lindquist, Erika A1 Lucas, Susan A1 Grimwood, Jane A1 Grigoriev, Igor V. A1 Kubicek, Christian P. A1 Martinez, Diego A1 van Peij, Noël N.M.E. A1 Roubos, Johannes A. A1 Nielsen, Jens A1 Baker, Scott E. T1 Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88 JF Genome Research JO Genome Research YR 2011 FD June 01 VO 21 IS 6 SP 885 OP 897 DO 10.1101/gr.112169.110 UL http://genome.cshlp.org/content/21/6/885.abstract AB The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook whole-genome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi.