Genomic hallmarks of parasexual reproduction in three hybrid groups of the human pathogen Cryptococcus neoformans
- 1Medical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life Sciences, Exeter EX4 4QD
Abstract
Hybridization is a major driver of fungal evolution, yet knowledge of the molecular mechanisms underpinning hybridization and its genomic impact remain limited. Here, we analyse 197 Cryptococcus neoformans genomic sequences, including 13 newly sequenced strains, identifying three genetically clustered and distinct hybrid groups (H1, H2 and H3) each with unique parental origins and ecological associations. Using phylogenomics, population structure analyses, and long-read genome assemblies, we identified hybrid genomes with chromosome-wide loss of heterozygosity (LOH), inheritance of large intact parental haplotype blocks and widespread aneuploidy within and across genomes. These patterns are also observed when progeny were generated with spo11{Delta} parents, indicating these features are a result of a meiotic-independent process such as parasex. This is further underscored by discovery of haploid and near-haploid recombinants in both spo11{Delta} mutant progeny and reanalysed wild-type hybrid progeny. We hypothesise these haploid and near-haploid recombinants are generated through ploidy reduction via independent chromosome assortment because of concerted chromosomal loss, which is a key feature of the parasexual cycle. Phenotypic assays demonstrated that several hybrid isolates have diverse growth and virulence patterns, underscoring functional consequences of genome plasticity. Together, our work suggests a non-meiotic reproductive process contributes to shape the genotypic and phenotypic diversity of Cryptococcus neoformans.
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BibTeX
@misc{anand2026genomic,
title = {{Genomic hallmarks of parasexual reproduction in three hybrid groups of the human pathogen Cryptococcus neoformans}},
author = {R. Anand and Q. Ma and D. Tamayo and G. Paul and N. Helmstetter and S. Sun and Z. Bian and K. J. Kwon-Chung and J. Heitman and R. A. Farrer},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.28.728413},
url = {https://www.biorxiv.org/content/10.64898/2026.05.28.728413v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Genomic hallmarks of parasexual reproduction in three hybrid groups of the human pathogen Cryptococcus neoformans
AU - R. Anand
AU - Q. Ma
AU - D. Tamayo
AU - G. Paul
AU - N. Helmstetter
AU - S. Sun
AU - Z. Bian
AU - K. J. Kwon-Chung
AU - J. Heitman
AU - R. A. Farrer
PY - 2026
DA - 2026/05/28
PB - bioRxiv
DO - 10.64898/2026.05.28.728413
UR - https://www.biorxiv.org/content/10.64898/2026.05.28.728413v2
AB - Hybridization is a major driver of fungal evolution, yet knowledge of the molecular mechanisms underpinning hybridization and its genomic impact remain limited. Here, we analyse 197 Cryptococcus neoformans genomic sequences, including 13 newly sequenced strains, identifying three genetically clustered and distinct hybrid groups (H1, H2 and H3) each with unique parental origins and ecological associations. Using phylogenomics, population structure analyses, and long-read genome assemblies, we identified hybrid genomes with chromosome-wide loss of heterozygosity (LOH), inheritance of large intact parental haplotype blocks and widespread aneuploidy within and across genomes. These patterns are also observed when progeny were generated with spo11{Delta} parents, indicating these features are a result of a meiotic-independent process such as parasex. This is further underscored by discovery of haploid and near-haploid recombinants in both spo11{Delta} mutant progeny and reanalysed wild-type hybrid progeny. We hypothesise these haploid and near-haploid recombinants are generated through ploidy reduction via independent chromosome assortment because of concerted chromosomal loss, which is a key feature of the parasexual cycle. Phenotypic assays demonstrated that several hybrid isolates have diverse growth and virulence patterns, underscoring functional consequences of genome plasticity. Together, our work suggests a non-meiotic reproductive process contributes to shape the genotypic and phenotypic diversity of Cryptococcus neoformans.
ER -