{"doi":"10.1101/2021.03.01.433394","title":"An evolutionary genomic approach reveals both conserved and species-specific genetic elements related to human disease in closely related <i>Aspergillus</i> fungi","abstract":"Abstract 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 non-pathogenic 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 non-pathogens. 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 hundreds of genes in pathogens that were faster-evolving than their orthologs in non-pathogens. For example, over 25% of all single-copy genes examined in A. fumigatus were faster-evolving. Functional testing of deletion mutants of 17 transcription factor-encoding genes whose evolution differed between pathogens and non-pathogens 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":224000,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":108920,"name":"Jacob L. Steenwyk","orcid":"0000-0002-8436-595X","position":1,"is_corresponding":false},{"id":329033,"name":"Lilian Pereira Silva","orcid":"0000-0002-0143-6557","position":2,"is_corresponding":false},{"id":565703,"name":"Patrícia Alves de Castro","orcid":"0000-0003-3045-6511","position":3,"is_corresponding":false},{"id":825783,"name":"Nauman Saeed","orcid":"0000-0003-3627-7725","position":4,"is_corresponding":false},{"id":825784,"name":"Falk Hillmann","orcid":"0000-0002-5493-930X","position":5,"is_corresponding":false},{"id":317398,"name":"Gustavo H. Goldman","orcid":"0000-0002-2986-350X","position":6,"is_corresponding":false},{"id":40922,"name":"Antonis Rokas","orcid":"0000-0002-7248-6551","position":7,"is_corresponding":false},{"id":329032,"name":"Matthew E. Mead","orcid":"0000-0001-9195-7585","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-18T23:54:14.760456Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}