Divergent Evolution of Early Terrestrial Fungi Reveals the Evolution of Mucormycosis Pathogenicity Factors

Abstract

Fungi have evolved over millions of years and their species diversity is predicted to be the second largest on the earth. Fungi have cross-kingdom interactions with many organisms which have mutually shaped their evolutionary trajectories. Zygomycete fungi hold a pivotal position in the fungal tree of life and provide important perspectives on the early evolution of fungi from aquatic to terrestrial environments. Phylogenomic analyses have found that zygomycete fungi diversified into two separate clades, the Mucoromycota which are frequently associated with plants and Zoopagomycota that are commonly animal-associated fungi. Genetic elements that contributed to the fitness and divergence of these lineages may have been shaped by the varied interactions these fungi have had with plants, animals, bacteria and other microbes. To investigate this, we performed comparative genomic analyses of the two clades of zygomycetes in the context of Kingdom Fungi, benefiting from our generation of a new collection of zygomycete genomes, including nine produced for this study. We identified lineage-specific genomic content which may contribute to the disparate biology observed in these zygomycetes. Our findings include the discovery of undescribed diversity in CotH, a Mucormycosis pathogenicity factor, which was found in a broad set of zygomycetes. Reconciliation analysis identified multiple duplication events and an expansion of CotH copies throughout the Mucoromycotina, Mortierellomycotina, Neocallimastigomycota, and Basidiobolus lineages. A kingdom-level phylogenomic analysis also identified new evolutionary relationships within the sub-phyla of Mucoromycota and Zoopagomycota, including supporting the sister-clade relationship between Glomeromycotina and Mortierellomycotina and the placement of Basidiobolus as sister to other Zoopagomycota lineages.

Genomic analysis ofAncylistes closterii, an enigmatic alga parasitic fungus in the arthropod-associated Entomophthoromycotina

“…The phylogenetic position of Basidiobolus has long been controversial despite large genome-scale phylogenies. The recent phylogenetic studies showed the same position as our analysis, the sister position to all other Zoopagomycota lineages (Galindo et al 2021; Strassert & Monaghan 2022; Wang et al 2023). However, some studies reported alternative positions such as sister to Entomophthoromycotina (Spatafora et al 2016; Wang et al 2020) and Mucoromycota (Li et al 2021).…”

“…Although the availability of genome data of zygomycete fungi is increasing, it tends to be biased toward Mucoromycota taxa, in which Mucorales (Mucoromycotina) taxa are especially rich in their genomic data (Gryganskyi et al 2023;Wang et al 2023). This taxonomic bias could be because they are generally saprotrophic and thus easy to be cultured, and some of them are causal agents of mucormycosis (Soare et al 2020).…”

“…The results supported a classification that divided zygomycete fungi into two phyla both of which include three subphyla: Mucoromycota (Glomeromycotina, Mortierellomycotina, Mucoromycotina) sister to Dikarya, and Zoopagomycota (Entomophthoromycotina, Kickxellomycotina, Zoopagomycotina) sister to Dikarya + Mucoromycota (Spatafora et al 2016). Although the availability of genome data of zygomycete fungi is increasing, it tends to be biased toward Mucoromycota taxa, in which Mucorales (Mucoromycotina) taxa are especially rich in their genomic data (Gryganskyi et al 2023; Wang et al 2023). This taxonomic bias could be because they are generally saprotrophic and thus easy to be cultured, and some of them are causal agents of mucormycosis (Soare et al 2020).…”

Computer-aided, resistance gene-guided genome mining for proteasome and HMG-CoA reductase inhibitors

“…2 ) contains two NRPS genes, a fatty-acyl-AMP ligase gene, a transporter gene, a TF gene, a proteasome β6 subunit homolog, and an esterase or lipase gene, the product of which is predicted to be involved in product release/transfer (Yeh et al, 2013 ). For one hit, in Amylomyces rouxii NRRL 5866 v1.0 (Wang et al, 2023 ), due to the presence of a large number of genes with unknown functions in the region, it was not obvious to us that the genes around the proteasome β6 formed an SM BGC. There were three hits in the Aspergillus multicolor v1.0 genome.…”

Sequencing the Genomes of the First Terrestrial Fungal Lineages: What Have We Learned?

“…Studies on metabolic patterns across the fungal kingdom, the search for the mating gene loci and protein families [ 81 , 82 , 83 ], and the phylogenies of certain taxonomic groups [ 84 , 85 ] have also been conducted using-whole genome sequencing data. Genome-based research has also provided insights into the trophic modes of zygomycete fungi, including the evolution of mycorrhizae [ 24 , 86 ] and commonalities in the pathogenicity of Mucoralean fungi [ 50 , 87 ].…”