An evolutionary genomic approach reveals both conserved and species-specific genetic elements related to human disease in closely related Aspergillus fungi.
Amoebozoa
/ microbiology
Animals
Aspergillosis
/ microbiology
Aspergillus
/ genetics
Disease Models, Animal
Evolution, Molecular
Fungal Proteins
/ genetics
Gene Expression Regulation, Fungal
Genome, Fungal
Genomics
Humans
Moths
/ microbiology
Phylogeny
Species Specificity
Transcription Factors
/ genetics
Virulence Factors
/ genetics
Aspergillus fumigatus
aspergillosis
convergent evolution
evolution
evolutionary rate
fungal disease
pathogenicity
virulence
Journal
Genetics
ISSN: 1943-2631
Titre abrégé: Genetics
Pays: United States
ID NLM: 0374636
Informations de publication
Date de publication:
24 06 2021
24 06 2021
Historique:
received:
11
03
2021
accepted:
20
04
2021
pubmed:
5
5
2021
medline:
22
2
2022
entrez:
4
5
2021
Statut:
ppublish
Résumé
Aspergillosis is an important opportunistic human disease caused by filamentous fungi in the genus Aspergillus. Roughly 70% of infections are caused by Aspergillus fumigatus, with the rest stemming from approximately a dozen other Aspergillus species. Several of these pathogens are closely related to A. fumigatus and belong in the same taxonomic section, section Fumigati. Pathogenic species are frequently most closely related to nonpathogenic ones, suggesting Aspergillus pathogenicity evolved multiple times independently. To understand the repeated evolution of Aspergillus pathogenicity, we performed comparative genomic analyses on 18 strains from 13 species, including 8 species in section Fumigati, which aimed to identify genes, both ones previously connected to virulence as well as ones never before implicated, whose evolution differs between pathogens and nonpathogens. We found that most genes were present in all species, including approximately half of those previously connected to virulence, but a few genes were section- or species-specific. Evolutionary rate analyses identified over 1700 genes whose evolutionary rate differed between pathogens and nonpathogens and dozens of genes whose rates differed between specific pathogens and the rest of the taxa. Functional testing of deletion mutants of 17 transcription factor-encoding genes whose evolution differed between pathogens and nonpathogens identified eight genes that affect either fungal survival in a model of phagocytic killing, host survival in an animal model of fungal disease, or both. These results suggest that the evolution of pathogenicity in Aspergillus involved both conserved and species-specific genetic elements, illustrating how an evolutionary genomic approach informs the study of fungal disease.
Identifiants
pubmed: 33944921
pii: 6263860
doi: 10.1093/genetics/iyab066
pmc: PMC8225353
pii:
doi:
Substances chimiques
Fungal Proteins
0
Transcription Factors
0
Virulence Factors
0
Banques de données
figshare
['10.6084/m9.figshare.14424386']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R56 AI146096
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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