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Title: Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi

Abstract

Fungi produce a wealth of pharmacologically bioactive secondary metabolites (SMs) from biosynthetic gene clusters (BGCs). It is common practice for drug discovery efforts to treat species’ secondary metabolomes as being well represented by a single or a small number of representative genomes. However, this approach misses the possibility that intraspecific population dynamics, such as adaptation to environmental conditions or local microbiomes, may harbor novel BGCs that contribute to the overall niche breadth of species. Using 94 isolates of Aspergillus flavus, a cosmopolitan model fungus, sampled from seven states in the United States, we dereplicate 7,821 BGCs into 92 unique BGCs. We find that more than 25% of pangenomic BGCs show population-specific patterns of presence/absence or protein divergence. Population-specific BGCs make up most of the accessory-genome BGCs, suggesting that different ecological forces that maintain accessory genomes may be partially mediated by population-specific differences in secondary metabolism. We use ultra-high-performance high-resolution mass spectrometry to confirm that these genetic differences in BGCs also result in chemotypic differences in SM production in different populations, which could mediate ecological interactions and be acted on by selection. Thus, our results suggest a paradigm shift that previously unrealized population-level reservoirs of SM diversity may be of significantmore » evolutionary, ecological, and pharmacological importance. Finally, we find that several population-specific BGCs from A. flavus are present in Aspergillus parasiticus and Aspergillus minisclerotigenes and discuss how the microevolutionary patterns we uncover inform macroevolutionary inferences and help to align fungal secondary metabolism with existing evolutionary theory.« less

Authors:
ORCiD logo [1]; ORCiD logo [2];  [3]; ORCiD logo [2];  [2]; ORCiD logo [4];  [5];  [6]; ORCiD logo [7]; ORCiD logo [2]; ORCiD logo [8]; ORCiD logo [9]
  1. Department of Bacteriology, University of Wisconsin–Madison, Madison, WI 53703,
  2. Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37830,
  3. Department of Genetics, University of Wisconsin–Madison, Madison, WI 53703,
  4. Department of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, United Kingdom,
  5. Department of Medical Microbiology and Immunology, University of Wisconsin–Madison, Madison, WI 53703,, Department of Plant Pathology, University of Wisconsin–Madison, Madison, WI 53706,
  6. Innovative Genomics Institute, University of California, Berkeley, CA 94720,
  7. Innovative Genomics Institute, University of California, Berkeley, CA 94720,, Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720,, Environmental Genomics and Systems Biology, The Lawrence Berkeley National Laboratory, Berkeley, CA 94720,
  8. School of Integrative Plant Science, Cornell University, Ithaca, NY 14853
  9. Department of Bacteriology, University of Wisconsin–Madison, Madison, WI 53703,, Department of Medical Microbiology and Immunology, University of Wisconsin–Madison, Madison, WI 53703,
Publication Date:
Research Org.:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); USDA
OSTI Identifier:
1847996
Alternate Identifier(s):
OSTI ID: 1785198
Grant/Contract Number:  
AC05-00OR22725; 2019-67012-29662
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 118 Journal Issue: 21; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; secondary metabolism; population genomics; allopatric speciation; eukaryotic; pangenome; comparative genomics

Citation Formats

Drott, Milton T., Rush, Tomás A., Satterlee, Tatum R., Giannone, Richard J., Abraham, Paul E., Greco, Claudio, Venkatesh, Nandhitha, Skerker, Jeffrey M., Glass, N. Louise, Labbé, Jesse L., Milgroom, Michael G., and Keller, Nancy P. Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi. United States: N. p., 2021. Web. doi:10.1073/pnas.2021683118.
Drott, Milton T., Rush, Tomás A., Satterlee, Tatum R., Giannone, Richard J., Abraham, Paul E., Greco, Claudio, Venkatesh, Nandhitha, Skerker, Jeffrey M., Glass, N. Louise, Labbé, Jesse L., Milgroom, Michael G., & Keller, Nancy P. Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi. United States. https://doi.org/10.1073/pnas.2021683118
Drott, Milton T., Rush, Tomás A., Satterlee, Tatum R., Giannone, Richard J., Abraham, Paul E., Greco, Claudio, Venkatesh, Nandhitha, Skerker, Jeffrey M., Glass, N. Louise, Labbé, Jesse L., Milgroom, Michael G., and Keller, Nancy P. Thu . "Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi". United States. https://doi.org/10.1073/pnas.2021683118.
@article{osti_1847996,
title = {Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi},
author = {Drott, Milton T. and Rush, Tomás A. and Satterlee, Tatum R. and Giannone, Richard J. and Abraham, Paul E. and Greco, Claudio and Venkatesh, Nandhitha and Skerker, Jeffrey M. and Glass, N. Louise and Labbé, Jesse L. and Milgroom, Michael G. and Keller, Nancy P.},
abstractNote = {Fungi produce a wealth of pharmacologically bioactive secondary metabolites (SMs) from biosynthetic gene clusters (BGCs). It is common practice for drug discovery efforts to treat species’ secondary metabolomes as being well represented by a single or a small number of representative genomes. However, this approach misses the possibility that intraspecific population dynamics, such as adaptation to environmental conditions or local microbiomes, may harbor novel BGCs that contribute to the overall niche breadth of species. Using 94 isolates of Aspergillus flavus, a cosmopolitan model fungus, sampled from seven states in the United States, we dereplicate 7,821 BGCs into 92 unique BGCs. We find that more than 25% of pangenomic BGCs show population-specific patterns of presence/absence or protein divergence. Population-specific BGCs make up most of the accessory-genome BGCs, suggesting that different ecological forces that maintain accessory genomes may be partially mediated by population-specific differences in secondary metabolism. We use ultra-high-performance high-resolution mass spectrometry to confirm that these genetic differences in BGCs also result in chemotypic differences in SM production in different populations, which could mediate ecological interactions and be acted on by selection. Thus, our results suggest a paradigm shift that previously unrealized population-level reservoirs of SM diversity may be of significant evolutionary, ecological, and pharmacological importance. Finally, we find that several population-specific BGCs from A. flavus are present in Aspergillus parasiticus and Aspergillus minisclerotigenes and discuss how the microevolutionary patterns we uncover inform macroevolutionary inferences and help to align fungal secondary metabolism with existing evolutionary theory.},
doi = {10.1073/pnas.2021683118},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 21,
volume = 118,
place = {United States},
year = {Thu May 20 00:00:00 EDT 2021},
month = {Thu May 20 00:00:00 EDT 2021}
}

Journal Article:
Free Publicly Available Full Text
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https://doi.org/10.1073/pnas.2021683118

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