A minimal Fanconi Anemia complex in early diverging fungi

Area of Science:

• Evolutionary biology
• Molecular genetics
• Mycology

Background:

• The Fanconi Anemia (FA) pathway is essential for resolving DNA interstrand crosslinks (ICLs) in vertebrates.
• While FA proteins are found in some fungi, their precise roles and evolutionary history remain unclear.
• Early diverging fungi (EDF) share more ancestral traits with animals compared to Dikarya.

Purpose of the Study:

• To trace the evolutionary trajectory of the FA pathway across Opisthokonta, focusing on fungi.
• To identify the presence and distribution of FA pathway homologs in fungal genomes.
• To investigate the functional conservation and potential degradation of the FA pathway in fungi.

Main Methods:

• Proteome-wide scanning for FA-related homologs across Opisthokonta.
• Phylogenetic analysis of identified FA gene families.
• Analysis of fungal gene transcription profiles under various conditions.
• Examination of genomic localization of FA genes.

Main Results:

• Fungal homologs of key FA pathway components, including activation and ID complexes, endonucleases, and deubiquitination proteins, were identified.
• All investigated fungi lack FANCC, FANCF, and FANCG, proteins vital for post-replication repair and chromosome stability in animals.
• A significant portion (21/32) of identified FA genes show upregulation in response to environmental stimuli, and several exhibit genomic co-localization.

Conclusions:

• The FA pathway appears to have undergone a gradual degradation from early diverging fungi to Dikarya.
• Early diverging fungi, particularly within Mucoromycota, may retain a functional, albeit minimal, FA pathway.
• The loss of specific FA proteins in Dikarya suggests a divergence in DNA repair mechanisms compared to animals.