The human fungal pathogen Aspergillus fumigatus can produce the highest known number of meiotic crossovers

Auxier, Ben; Debets, Alfons J.M.; Rhodes, Johanna; Stanford, Felicia Adelina; Becker, Frank M.; Marquez, Francisca Reyes; Nijland, Reindert; Dyer, Paul S.; Fisher, Matthew C.; den Heuvel, Joost van; Snelders, Eveline

Abstract

Sexual reproduction involving meiosis is essential in most eukaryotes. This produces offspring with novel genotypes, both by segregation of parental chromosomes as well as crossovers between homologous chromosomes. A sexual cycle for the opportunistic human pathogenic fungus Aspergillus fumigatus is known, but the genetic consequences of meiosis have remained unknown. Among other Aspergilli, it is known that A. flavus has a moderately high recombination rate with an average of 4.2 crossovers per chromosome pair, whereas A. nidulans has in contrast a higher rate with 9.3 crossovers per chromosome pair. Here, we show in a cross between A. fumigatus strains that they produce an average of 29.9 crossovers per chromosome pair and large variation in total map length across additional strain crosses. This rate of crossovers per chromosome is more than twice that seen for any known organism, which we discuss in relation to other genetic model systems. We validate this high rate of crossovers through mapping of resistance to the laboratory antifungal acriflavine by using standing variation in an undescribed ABC efflux transporter. We then demonstrate that this rate of crossovers is sufficient to produce one of the common multidrug resistant haplotypes found in the cyp51A gene (TR34/L98H) in crosses among parents harboring either of 2 nearby genetic variants, possibly explaining the early spread of such haplotypes. Our results suggest that genomic studies in this species should reassess common assumptions about linkage between genetic regions. The finding of an unparalleled crossover rate in A. fumigatus provides opportunities to understand why these rates are not generally higher in other eukaryotes. [Abstract copyright: Copyright: © 2023 Auxier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.]

Citation

Auxier, B., Debets, A. J., Rhodes, J., Stanford, F. A., Becker, F. M., Marquez, F. R., Nijland, R., Dyer, P. S., Fisher, M. C., den Heuvel, J. V., & Snelders, E. (2023). The human fungal pathogen Aspergillus fumigatus can produce the highest known number of meiotic crossovers. PLoS Biology, 21(9), Article e3002278. https://doi.org/10.1371/journal.pbio.3002278

• Journal Article Type: Article
• Acceptance Date: Jul 27, 2023
• Online Publication Date: Sep 14, 2023
• Publication Date: Sep 14, 2023
• Deposit Date: Sep 29, 2023
• Publicly Available Date: Oct 3, 2023
• Journal: PLOS Biology
• Print ISSN: 1544-9173
• Electronic ISSN: 1545-7885
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 21
• Issue: 9
• Article Number: e3002278
• DOI: https://doi.org/10.1371/journal.pbio.3002278
• Keywords: Biological Transport, Humans, Eukaryota, Meiosis - genetics, ATP-Binding Cassette Transporters, Aspergillus fumigatus - genetics, Antifungal Agents
• Public URL: https://nottingham-repository.worktribe.com/output/25394299
• Publisher URL: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002278