{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:19:57Z","timestamp":1768508397398,"version":"3.49.0"},"posted":{"date-parts":[[2017,6,13]]},"group-title":"Genomics","reference-count":96,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T00:00:00Z","timestamp":1497312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2017,10,23]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Filamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen\n                  <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                  . Investigation of genome-wide within-species variation revealed five general types of variation in SM gene clusters: non-functional gene polymorphisms, gene gain and loss polymorphisms, whole cluster gain and loss polymorphisms, allelic polymorphisms where different alleles corresponded to distinct, non-homologous clusters, and location polymorphisms in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid, as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms whose detection requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and non-homologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, genomic deletion and insertion events, as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.\n                <\/jats:p>","DOI":"10.1101\/149856","type":"posted-content","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T02:55:16Z","timestamp":1497408916000},"source":"Crossref","is-referenced-by-count":29,"title":["Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9579-4178","authenticated-orcid":false,"given":"Abigail L.","family":"Lind","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6843-5906","authenticated-orcid":false,"given":"Jennifer H.","family":"Wisecaver","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Lameiras","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7983-2218","authenticated-orcid":false,"given":"Philipp","family":"Wiemann","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0929-3658","authenticated-orcid":false,"given":"Jonathan M.","family":"Palmer","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4386-9473","authenticated-orcid":false,"given":"Nancy P.","family":"Keller","sequence":"additional","affiliation":[]},{"given":"Fernando","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Gustavo H.","family":"Goldman","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7248-6551","authenticated-orcid":false,"given":"Antonis","family":"Rokas","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2024080312441529000_149856v3.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.44.100190.002143"},{"key":"2024080312441529000_149856v3.2","doi-asserted-by":"crossref","unstructured":"Schimek C. Evolution of Special Metabolism in Fungi?: Concepts, Mechanisms, and Pathways. In: P\u00f6ggler S , W\u00f6stmeyer J , editors. Evolution of Fungi and Fungal-Like Organisms, The Mycota. XIV. Berlin, Heidelberg: Springer-Verlag; 2011. pp. 293\u2013328.","DOI":"10.1007\/978-3-642-19974-5_13"},{"key":"2024080312441529000_149856v3.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2008.10.007"},{"key":"2024080312441529000_149856v3.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.l003859"},{"key":"2024080312441529000_149856v3.5","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2007.2044"},{"key":"2024080312441529000_149856v3.6","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.l897"},{"key":"2024080312441529000_149856v3.7","unstructured":"Bennett J , Bentley R. What\u2019s in a name?\u2014Microbial secondary metabolism. Adv Appl Microbiol. 1989;34. 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