A minimal Fanconi Anemia complex in Early Diverging Fungi

Abstract Background: Fanconi Anemia (FA) pathway resolves DNA interstrand cross links (ICL), the phenomenon preventing separation of DNA strands and blocking transcription and replication. A typical FA pathway in humans consists of six protein complexes working in an orchestrated manner. This pathway was initially recognized only in vertebrates, but later on was also confirmed in other animals and speculated in fungi. For instance, FANCM, FANCL and FANCJ proteins are present in Saccharomyces cerevisiae but at the same time, their mechanism of interaction to resolve ICL is still unclear. Unlike Dikarya, early diverging fungi possess more traits shared with animals. In this work, we trace the evolutionary history of FA pathway genes across Opisthokonta. We scanned complete proteomes for FA-related homologs to establish their taxonomic distribution and analyzed their phylogenetic trees to trace evolutionary events. We checked transcription profiles of FA genes to test if they respond to environmental conditions and their genomic localizations for potential co-localization. Results: We identified fungal homologs of the activation and ID complex, 6 out of 13 core proteins, all of the endonucleases, and deubiquitination proteins. All fungal taxa lack FANCC, FANCF and FANCG proteins responsible for post-replication repair and chromosome stability in animals. The observed taxonomic distribution of the FA components can be attributed to a gradual degradation of the pathway from early diverging fungi (EDF) to Dikarya. One of the key differences is that EDF have the ID complex responsible for recruiting endonucleases to the site of DNA damage. Moreover, 20 out of 26 identified FA genes are not only expressed but also upregulated in response to different growth conditions. We observed that several genes encoding FA proteins are co-localized in fungal genomes which also could facilitate co-expression. Conclusions: Our results indicate that EDF share another ancestral eukaryotic trait with their sister evolutionary group, animals. A minimal FA pathway might still be functional in Mucoromycota with a gradual loss of components in Dikarya ancestors.