title: Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88.
abstract: 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.
authors.affiliation: Center for Microbial Biotechnology, Department of Systems Biology, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Mikael R
authors.initials: MR
authors.lastname: Andersen
authors.forename: Margarita P
authors.initials: MP
authors.lastname: Salazar
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schaap
authors.forename: Peter J I
authors.initials: PJ
authors.lastname: van de Vondervoort
authors.forename: David
authors.initials: D
authors.lastname: Culley
authors.forename: Jette
authors.initials: J
authors.lastname: Thykaer
authors.forename: Jens C
authors.initials: JC
authors.lastname: Frisvad
authors.forename: Kristian F
authors.initials: KF
authors.lastname: Nielsen
authors.forename: Richard
authors.initials: R
authors.lastname: Albang
authors.forename: Kaj
authors.initials: K
authors.lastname: Albermann
authors.forename: Randy M
authors.initials: RM
authors.lastname: Berka
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Braus
authors.forename: Susanna A
authors.initials: SA
authors.lastname: Braus-Stromeyer
authors.forename: Luis M
authors.initials: LM
authors.lastname: Corrochano
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Dai
authors.forename: Piet W M
authors.initials: PW
authors.lastname: van Dijck
authors.forename: Gerald
authors.initials: G
authors.lastname: Hofmann
authors.forename: Linda L
authors.initials: LL
authors.lastname: Lasure
authors.forename: Jon K
authors.initials: JK
authors.lastname: Magnuson
authors.forename: Hildegard
authors.initials: H
authors.lastname: Menke
authors.forename: Martin
authors.initials: M
authors.lastname: Meijer
authors.forename: Susan L
authors.initials: SL
authors.lastname: Meijer
authors.forename: Jakob B
authors.initials: JB
authors.lastname: Nielsen
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nielsen
authors.forename: Albert J J
authors.initials: AJ
authors.lastname: van Ooyen
authors.forename: Herman J
authors.initials: HJ
authors.lastname: Pel
authors.forename: Lars
authors.initials: L
authors.lastname: Poulsen
authors.forename: Rob A
authors.initials: RA
authors.lastname: Samson
authors.forename: Hein
authors.initials: H
authors.lastname: Stam
authors.forename: Adrian
authors.initials: A
authors.lastname: Tsang
authors.forename: Johannes M
authors.initials: JM
authors.lastname: van den Brink
authors.forename: Alex
authors.initials: A
authors.lastname: Atkins
authors.forename: Andrea
authors.initials: A
authors.lastname: Aerts
authors.forename: Harris
authors.initials: H
authors.lastname: Shapiro
authors.forename: Jasmyn
authors.initials: J
authors.lastname: Pangilinan
authors.forename: Asaf
authors.initials: A
authors.lastname: Salamov
authors.forename: Yigong
authors.initials: Y
authors.lastname: Lou
authors.forename: Erika
authors.initials: E
authors.lastname: Lindquist
authors.forename: Susan
authors.initials: S
authors.lastname: Lucas
authors.forename: Jane
authors.initials: J
authors.lastname: Grimwood
authors.forename: Igor V
authors.initials: IV
authors.lastname: Grigoriev
authors.forename: Christian P
authors.initials: CP
authors.lastname: Kubicek
authors.forename: Diego
authors.initials: D
authors.lastname: Martinez
authors.forename: Noël N M E
authors.initials: NN
authors.lastname: van Peij
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Roubos
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
authors.forename: Scott E
authors.initials: SE
authors.lastname: Baker
mesh_terms: D001234:Aspergillus niger / Q000235:genetics*; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D015321:Gene Rearrangement / Q000235:genetics; D022761:Gene Transfer, Horizontal / Q000235:genetics; D014644:Genetic Variation; D016681:Genome, Fungal / Q000235:genetics*; D023281:Genomics / Q000379:methods; D008969:Molecular Sequence Data; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D026801:Synteny / Q000235:genetics