Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants

Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Isidro Álvarez-Escribano [verfasserIn] Christoph Sasse [verfasserIn] Jin Woo Bok [verfasserIn] Hyunsoo Na [verfasserIn] Mojgan Amirebrahimi [verfasserIn] Anna Lipzen [verfasserIn] Wendy Schackwitz [verfasserIn] Joel Martin [verfasserIn] Kerrie Barry [verfasserIn] Gabriel Gutiérrez [verfasserIn] Sara Cea-Sánchez [verfasserIn] Ana T. Marcos [verfasserIn] Igor V. Grigoriev [verfasserIn] Nancy P. Keller [verfasserIn] Gerhard H. Braus [verfasserIn] David Cánovas [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Aspergillus Aflatoxin Mutation accumulating lines Genome stability Non-homologous end-joining ku70

Übergeordnetes Werk:	In: BMC Biology - BMC, 2003, 17(2019), 1, Seite 17
Übergeordnetes Werk:	volume:17 ; year:2019 ; number:1 ; pages:17

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12915-019-0702-0

Katalog-ID:	DOAJ048312991

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245	1	0	\|a Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants
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520			\|a Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified.
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700	0		\|a Jin Woo Bok \|e verfasserin \|4 aut
700	0		\|a Hyunsoo Na \|e verfasserin \|4 aut
700	0		\|a Mojgan Amirebrahimi \|e verfasserin \|4 aut
700	0		\|a Anna Lipzen \|e verfasserin \|4 aut
700	0		\|a Wendy Schackwitz \|e verfasserin \|4 aut
700	0		\|a Joel Martin \|e verfasserin \|4 aut
700	0		\|a Kerrie Barry \|e verfasserin \|4 aut
700	0		\|a Gabriel Gutiérrez \|e verfasserin \|4 aut
700	0		\|a Sara Cea-Sánchez \|e verfasserin \|4 aut
700	0		\|a Ana T. Marcos \|e verfasserin \|4 aut
700	0		\|a Igor V. Grigoriev \|e verfasserin \|4 aut
700	0		\|a Nancy P. Keller \|e verfasserin \|4 aut
700	0		\|a Gerhard H. Braus \|e verfasserin \|4 aut
700	0		\|a David Cánovas \|e verfasserin \|4 aut
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author_variant	i á e iáe c s cs j w b jwb h n hn m a ma a l al w s ws j m jm k b kb g g gg s c s scs a t m atm i v g ivg n p k npk g h b ghb d c dc
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allfields	10.1186/s12915-019-0702-0 doi (DE-627)DOAJ048312991 (DE-599)DOAJ76866503b45a4e649e06953c80fdc6fd DE-627 ger DE-627 rakwb eng QH301-705.5 Isidro Álvarez-Escribano verfasserin aut Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified. Aspergillus Aflatoxin Mutation accumulating lines Genome stability Non-homologous end-joining ku70 Biology (General) Christoph Sasse verfasserin aut Jin Woo Bok verfasserin aut Hyunsoo Na verfasserin aut Mojgan Amirebrahimi verfasserin aut Anna Lipzen verfasserin aut Wendy Schackwitz verfasserin aut Joel Martin verfasserin aut Kerrie Barry verfasserin aut Gabriel Gutiérrez verfasserin aut Sara Cea-Sánchez verfasserin aut Ana T. Marcos verfasserin aut Igor V. Grigoriev verfasserin aut Nancy P. Keller verfasserin aut Gerhard H. Braus verfasserin aut David Cánovas verfasserin aut In BMC Biology BMC, 2003 17(2019), 1, Seite 17 (DE-627)377757241 (DE-600)2133020-7 17417007 nnns volume:17 year:2019 number:1 pages:17 https://doi.org/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/article/76866503b45a4e649e06953c80fdc6fd kostenfrei http://link.springer.com/article/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/toc/1741-7007 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 17
spelling	10.1186/s12915-019-0702-0 doi (DE-627)DOAJ048312991 (DE-599)DOAJ76866503b45a4e649e06953c80fdc6fd DE-627 ger DE-627 rakwb eng QH301-705.5 Isidro Álvarez-Escribano verfasserin aut Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified. Aspergillus Aflatoxin Mutation accumulating lines Genome stability Non-homologous end-joining ku70 Biology (General) Christoph Sasse verfasserin aut Jin Woo Bok verfasserin aut Hyunsoo Na verfasserin aut Mojgan Amirebrahimi verfasserin aut Anna Lipzen verfasserin aut Wendy Schackwitz verfasserin aut Joel Martin verfasserin aut Kerrie Barry verfasserin aut Gabriel Gutiérrez verfasserin aut Sara Cea-Sánchez verfasserin aut Ana T. Marcos verfasserin aut Igor V. Grigoriev verfasserin aut Nancy P. Keller verfasserin aut Gerhard H. Braus verfasserin aut David Cánovas verfasserin aut In BMC Biology BMC, 2003 17(2019), 1, Seite 17 (DE-627)377757241 (DE-600)2133020-7 17417007 nnns volume:17 year:2019 number:1 pages:17 https://doi.org/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/article/76866503b45a4e649e06953c80fdc6fd kostenfrei http://link.springer.com/article/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/toc/1741-7007 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 17
allfields_unstemmed	10.1186/s12915-019-0702-0 doi (DE-627)DOAJ048312991 (DE-599)DOAJ76866503b45a4e649e06953c80fdc6fd DE-627 ger DE-627 rakwb eng QH301-705.5 Isidro Álvarez-Escribano verfasserin aut Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified. Aspergillus Aflatoxin Mutation accumulating lines Genome stability Non-homologous end-joining ku70 Biology (General) Christoph Sasse verfasserin aut Jin Woo Bok verfasserin aut Hyunsoo Na verfasserin aut Mojgan Amirebrahimi verfasserin aut Anna Lipzen verfasserin aut Wendy Schackwitz verfasserin aut Joel Martin verfasserin aut Kerrie Barry verfasserin aut Gabriel Gutiérrez verfasserin aut Sara Cea-Sánchez verfasserin aut Ana T. Marcos verfasserin aut Igor V. Grigoriev verfasserin aut Nancy P. Keller verfasserin aut Gerhard H. Braus verfasserin aut David Cánovas verfasserin aut In BMC Biology BMC, 2003 17(2019), 1, Seite 17 (DE-627)377757241 (DE-600)2133020-7 17417007 nnns volume:17 year:2019 number:1 pages:17 https://doi.org/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/article/76866503b45a4e649e06953c80fdc6fd kostenfrei http://link.springer.com/article/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/toc/1741-7007 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 17
allfieldsGer	10.1186/s12915-019-0702-0 doi (DE-627)DOAJ048312991 (DE-599)DOAJ76866503b45a4e649e06953c80fdc6fd DE-627 ger DE-627 rakwb eng QH301-705.5 Isidro Álvarez-Escribano verfasserin aut Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified. Aspergillus Aflatoxin Mutation accumulating lines Genome stability Non-homologous end-joining ku70 Biology (General) Christoph Sasse verfasserin aut Jin Woo Bok verfasserin aut Hyunsoo Na verfasserin aut Mojgan Amirebrahimi verfasserin aut Anna Lipzen verfasserin aut Wendy Schackwitz verfasserin aut Joel Martin verfasserin aut Kerrie Barry verfasserin aut Gabriel Gutiérrez verfasserin aut Sara Cea-Sánchez verfasserin aut Ana T. Marcos verfasserin aut Igor V. Grigoriev verfasserin aut Nancy P. Keller verfasserin aut Gerhard H. Braus verfasserin aut David Cánovas verfasserin aut In BMC Biology BMC, 2003 17(2019), 1, Seite 17 (DE-627)377757241 (DE-600)2133020-7 17417007 nnns volume:17 year:2019 number:1 pages:17 https://doi.org/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/article/76866503b45a4e649e06953c80fdc6fd kostenfrei http://link.springer.com/article/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/toc/1741-7007 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 17
allfieldsSound	10.1186/s12915-019-0702-0 doi (DE-627)DOAJ048312991 (DE-599)DOAJ76866503b45a4e649e06953c80fdc6fd DE-627 ger DE-627 rakwb eng QH301-705.5 Isidro Álvarez-Escribano verfasserin aut Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified. Aspergillus Aflatoxin Mutation accumulating lines Genome stability Non-homologous end-joining ku70 Biology (General) Christoph Sasse verfasserin aut Jin Woo Bok verfasserin aut Hyunsoo Na verfasserin aut Mojgan Amirebrahimi verfasserin aut Anna Lipzen verfasserin aut Wendy Schackwitz verfasserin aut Joel Martin verfasserin aut Kerrie Barry verfasserin aut Gabriel Gutiérrez verfasserin aut Sara Cea-Sánchez verfasserin aut Ana T. Marcos verfasserin aut Igor V. Grigoriev verfasserin aut Nancy P. Keller verfasserin aut Gerhard H. Braus verfasserin aut David Cánovas verfasserin aut In BMC Biology BMC, 2003 17(2019), 1, Seite 17 (DE-627)377757241 (DE-600)2133020-7 17417007 nnns volume:17 year:2019 number:1 pages:17 https://doi.org/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/article/76866503b45a4e649e06953c80fdc6fd kostenfrei http://link.springer.com/article/10.1186/s12915-019-0702-0 kostenfrei https://doaj.org/toc/1741-7007 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 17
language	English
source	In BMC Biology 17(2019), 1, Seite 17 volume:17 year:2019 number:1 pages:17
sourceStr	In BMC Biology 17(2019), 1, Seite 17 volume:17 year:2019 number:1 pages:17
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Aspergillus Aflatoxin Mutation accumulating lines Genome stability Non-homologous end-joining ku70 Biology (General)
isfreeaccess_bool	true
container_title	BMC Biology
authorswithroles_txt_mv	Isidro Álvarez-Escribano @@aut@@ Christoph Sasse @@aut@@ Jin Woo Bok @@aut@@ Hyunsoo Na @@aut@@ Mojgan Amirebrahimi @@aut@@ Anna Lipzen @@aut@@ Wendy Schackwitz @@aut@@ Joel Martin @@aut@@ Kerrie Barry @@aut@@ Gabriel Gutiérrez @@aut@@ Sara Cea-Sánchez @@aut@@ Ana T. Marcos @@aut@@ Igor V. Grigoriev @@aut@@ Nancy P. Keller @@aut@@ Gerhard H. Braus @@aut@@ David Cánovas @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	377757241
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These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. 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callnumber-first	Q - Science
author	Isidro Álvarez-Escribano
spellingShingle	Isidro Álvarez-Escribano misc QH301-705.5 misc Aspergillus misc Aflatoxin misc Mutation accumulating lines misc Genome stability misc Non-homologous end-joining misc ku70 misc Biology (General) Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants
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topic_title	QH301-705.5 Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants Aspergillus Aflatoxin Mutation accumulating lines Genome stability Non-homologous end-joining ku70
topic	misc QH301-705.5 misc Aspergillus misc Aflatoxin misc Mutation accumulating lines misc Genome stability misc Non-homologous end-joining misc ku70 misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc Aspergillus misc Aflatoxin misc Mutation accumulating lines misc Genome stability misc Non-homologous end-joining misc ku70 misc Biology (General)
topic_browse	misc QH301-705.5 misc Aspergillus misc Aflatoxin misc Mutation accumulating lines misc Genome stability misc Non-homologous end-joining misc ku70 misc Biology (General)
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title	Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants
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title_full	Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants
author_sort	Isidro Álvarez-Escribano
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author_browse	Isidro Álvarez-Escribano Christoph Sasse Jin Woo Bok Hyunsoo Na Mojgan Amirebrahimi Anna Lipzen Wendy Schackwitz Joel Martin Kerrie Barry Gabriel Gutiérrez Sara Cea-Sánchez Ana T. Marcos Igor V. Grigoriev Nancy P. Keller Gerhard H. Braus David Cánovas
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author-letter	Isidro Álvarez-Escribano
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title_sort	genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in a. flavus, and sexual aberrancy in non-homologous end-joining mutants
callnumber	QH301-705.5
title_auth	Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants
abstract	Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified.
abstractGer	Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified.
abstract_unstemmed	Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified.
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title_short	Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants
url	https://doi.org/10.1186/s12915-019-0702-0 https://doaj.org/article/76866503b45a4e649e06953c80fdc6fd http://link.springer.com/article/10.1186/s12915-019-0702-0 https://doaj.org/toc/1741-7007
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author2	Christoph Sasse Jin Woo Bok Hyunsoo Na Mojgan Amirebrahimi Anna Lipzen Wendy Schackwitz Joel Martin Kerrie Barry Gabriel Gutiérrez Sara Cea-Sánchez Ana T. Marcos Igor V. Grigoriev Nancy P. Keller Gerhard H. Braus David Cánovas
author2Str	Christoph Sasse Jin Woo Bok Hyunsoo Na Mojgan Amirebrahimi Anna Lipzen Wendy Schackwitz Joel Martin Kerrie Barry Gabriel Gutiérrez Sara Cea-Sánchez Ana T. Marcos Igor V. Grigoriev Nancy P. Keller Gerhard H. Braus David Cánovas
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callnumber-subject	QH - Natural History and Biology
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doi_str	10.1186/s12915-019-0702-0
callnumber-a	QH301-705.5
up_date	2024-07-03T17:06:06.145Z
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These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. 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Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants

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