Pan-genome analyses of model fungal species

Abstract

The concept of the species 'pan-genome', the union of 'core' conserved genes and all 'accessory' non-conserved genes across all strains of a species, was first proposed in prokaryotes to account for intraspecific variability. Species pan-genomes have been extensively studied in prokaryotes, but evidence of species pan-genomes has also been demonstrated in eukaryotes such as plants and fungi. Using a previously published methodology based on sequence homology and conserved microsynteny, in addition to bespoke pipelines, we have investigated the pan-genomes of four model fungal species: Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans var. grubii and Aspergillus fumigatus. Between 80 and 90 % of gene models per strain in each of these species are core genes that are highly conserved across all strains of that species, many of which are involved in housekeeping and conserved survival processes. In many of these species, the remaining 'accessory' gene models are clustered within subterminal regions and may be involved in pathogenesis and antimicrobial resistance. Analysis of the ancestry of species core and accessory genomes suggests that fungal pan-genomes evolve by strain-level innovations such as gene duplication as opposed to wide-scale horizontal gene transfer. Our findings lend further supporting evidence to the existence of species pan-genomes in eukaryote taxa.

Keywords: Aspergillus; Cryptococcus; comparative genomics; fungal pangenomes; yeast.

Fig. 1.

Seven-set Venn diagram representing a hypothetical species pan-genome. Each set represents genes/gene models conserved across strains of a given species. The core species genome (grey) is defined as the set of all genes/gene models conserved across all strains of a species, while the accessory genome consists of all genes/gene models not universally conserved within a species.

Fig. 2.

Approximate maximum-likelihood supermatrix phylogeny of the Saccharomyces cerevisiae pan-genome dataset based on 4311 core orthologue clusters. Saccharomyces cerevisiae populations are as assigned by Strope et al., clinical strains are indicated by red branches. Numbers below branches refer to Shimodaira–Hasegawa local supports, maximum supports are indicated by asterisks. Dollo parsimony analysis of gene model gain/loss events is annotated above branches in green and orange, respectively.

Fig. 3.

Approximate maximum-likelihood supermatrix phylogeny of the Candida albicans pan-genome dataset based on 4327 core orthologue clusters. Numbers below branches refer to Shimodaira–Hasegawa local supports, maximum supports are indicated by asterisks. Dollo parsimony analysis of gene model gain/loss events is annotated above branches in green and orange, respectively.

Fig. 4.

Approximate maximum-likelihood supermatrix phylogeny of the Cryptococcus neoformans var. grubii pan-genome dataset based on 4512 core orthologue clusters. Numbers below branches refer to Shimodaira–Hasegawa local supports, maximum supports are indicated by asterisks. Dollo parsimony analysis of gene model gain/loss events is annotated above branches in green and orange, respectively.

Fig. 5.

Approximate maximum-likelihood supermatrix phylogeny of the Aspergillus fumigatus pan-genome dataset based on 5724 core orthologue clusters. Numbers below branches refer to Shimodaira–Hasegawa local supports, maximum supports are indicated by asterisks. Dollo parsimony analysis of gene model gain/loss events is annotated above branches in green and orange, respectively.

Fig. 6.

Pan-genomes of four fungal species. (a) Saccharomyces cerevisiae, (b) Candida albicans, (c) Cryptococcus neoformans var. grubii, (d) Aspergillus fumigatus. The ring charts represent the total number of gene models in pan-genome complements expressed as a proportion of total pan-genome size. Sections in dark-red represent duplicated core gene models in the accessory genome.