Evolution of the human pathogenic lifestyle in fungi

Abstract

Fungal pathogens cause more than a billion human infections every year, resulting in more than 1.6 million deaths annually. Understanding the natural history and evolutionary ecology of fungi is helping us understand how disease-relevant traits have repeatedly evolved. Different types and mechanisms of genetic variation have contributed to the evolution of fungal pathogenicity and specific genetic differences distinguish pathogens from non-pathogens. Insights into the traits, genetic elements, and genetic and ecological mechanisms that contribute to the evolution of fungal pathogenicity are crucial for developing strategies to both predict emergence of fungal pathogens and develop drugs to combat them.

Figure 1.

Milestones in the study of fungal diseases.

Figure 1.

Milestones in the study of fungal diseases.

Figure 1.

Milestones in the study of fungal diseases.

Figure 2.. Human pathogenicity has repeatedly evolved in fungi.

Genera and lineages harboring major and emerging fungal pathogens (see Table 1) are shown in red and non-pathogenic taxa are shown in black. The fungal tree of life based on a phylogenomic analysis of 1,644 species and 290 genes from Ref.. Only species whose genomes have been sequenced are included. The tree with species names included is shown in Figure S1. Figure adapted with permission from ref. , Elsevier.

Figure 3.. Repeated evolution of pathogenicity in Aspergillus section Fumigati lineage.

Species whose biosafety level (BSL) is 2 are considered pathogenic and shown in red. BSL1 organisms are shown in black. Estimated cases of invasive infection (K: in thousands) / year (y) are also shown. Phylogeny modified from^,–; infection case estimates from^,. Figure adapted with permission from ref. , under a Creative Commons license CC BY 4.0.

Figure 4.. Genetic variation and the evolution of infection-relevant traits.

Some of the types of genetic variation illustrated typically affect large genomic regions or entire genomes; these include (A) variation in ploidy, (B) loss of heterozygosity, (C) transposon mobilization, (D) introgression, and (E) hybridization. Note that the red branch leading to taxon D in the hybridization panel is meant to illustrate the origin of a new hybrid. Other types of variation typically affect a single locus; these include (F) copy number variation, (G) horizontal gene transfer, (H) single nucleotide polymorphisms, (I) cis-regulatory element variation, and (J) gene duplication and loss. Copy number variation could involve linear or circular DNA. Most examples of genetic variation concerning the evolution of human fungal pathogens identified focus on or concern variation in the protein-coding regions of the genome. However, variation of cis-regulatory elements (panel I), which can alter gene activity, can also have a major impact in fungal pathogen evolution. We currently lack understanding of the relative frequency with which these mechanisms operate in different fungal pathogens. It is also likely that these mechanisms differ in their prevalence in fungal genomes. Figure adapted with permission from: a,b, ref. , American Society for Microbiology; c, ref. , Springer Nature Ltd; d,e, ref. , Springer Nature Ltd; f, reprinted courtesy of the National Human Genome Research Institute, https://www.genome.gov; g, ref. , Springer Nature Ltd; h, ref. , Springer Nature Ltd; i, ref. , under a Creative Commons license CC BY 4.0; j, ref. , under a Creative Commons license CC BY 4.0.