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.

Massive gene presence/absence variation in the mussel genome as an adaptive strategy: first evidence of a pan-genome in Metazoa

“…Remarkably, most dispensable genes belonged to Mytilusspecific expanded families, and were enriched in functions related with protein/carbohydrate recognition and survival, suggesting a potential role of PAV in the evolutionary success of this cosmopolitan marine invertebrate. This unexpected discovery represents the first evidence of widespread PAV in a metazoan, extending the concept of pan-genome, so far only considered as a relevant phenomenon in viruses, prokaryotes and a few fungi and plants (15)(16)(17)(18)(19)(20)(21)(22), to the animal kingdom.…”

“…The pan-genome architecture of the coccolithophore Emiliania huxley is thought to have an adaptive value, explaining its cosmopolitan oceanic distribution and ability to thrive in different habitats, due to acquisition of accessory metabolic activities provided by dispensable genes (35). Recent studies have also revealed the fundamental role of dispensable genes in increasing the pathogenic potential and antimicrobial resistance in fungi (21,22).…”

“…Whether the pan-genomic architecture of the mussel genome provides a selective advantage at the population level is a fundamental question. In other organisms, dispensable genes can be beneficial, for example enhancing the ability to acquire novel metabolic pathways (e.g., bacteria) (18), to migrate to new ecological niches (e.g., bacteria and unicellular algae) (35) or to enhance the ability to interact with a host (e.g., viruses and fungal pathogens) (20)(21)(22). In our opinion, the large over-representation of genes involved in the response to stress and survival in the variable fraction of the mussel pan-genome (Supplementary Data Note 15) and the impact of PAV on the molecular diversification of AMPs (Figure 4B, Supplementary Data Note 18) strongly suggest an adaptive role for the pan-genomic architecture.…”

Multi-epitope Peptide Vaccine Prediction for Candida albicans targeting Pyruvate Kinase Protein; an Immunoinformatics Approach

“…In addition, Disseminated invasive candidiasis that is a major complication of the disease has an estimated mortality rate of 40%-60% even with the use of antifungal drugs. 1-5 it occurs with various other manifestations ranging from vaginal infections, which affect up to 75% of the women at least once in their lifetime, to deep systemic infections in hospitalized patients leading to high morbidity and mortality rates specially, in immunocompromised individuals, including organ recipients and HIV patients 1,2, [6][7][8][9][10][11][12][13] Three proteins are most likely to be immunogenic in candida albicans which are the fructose-bisphosphate aldolase (Fba1), the phosphoglycerate kinase (Pgk) and the pyruvate kinase (Pk) with (pk) and (Fba1) being more immunodominant . 11,14 PK a 504 bp long, highly conservative protein which catalyzes the final step in glycolysis, converting phosphoenolpyruvate (PEP) and adenosine diphosphate (ADP) to pyruvate and adenosine triphosphate (ATP), once pyruvate is synthesized; it is either fed into the tri-carboxylic acid (TCA) cycle for oxidative phosphorylation or reduced to lactate under anaerobic conditions by lactate dehydrogenase enzyme LDH.…”

The Collaborative Cross Graphical Genome

“…Moreover, we refer to traditional single sequence reference assemblies as linear reference genomes. Reference pangenomes are already available for viral and prokaryotic strains and populations (Tettelin et al 2005;Hogg et al 2007;Lefebure and Stanhope 2007;Jacobsen et al 2011;Zhou et al 2018), but are less common for eukaryotes (Li et al 2010;Hu et al 2017;Peter et al 2018;Tian et al 2018;McCarthy and Fitzpatrick 2019). Common pangenome representations includes multiple sequence alignments, kmer-based, or graphs.…”