Phylogenomics of caspase-activated DNA fragmentation factor

Area of Science:

• Cellular Biology
• Evolutionary Biology
• Genomics

Background:

• Apoptosis, or programmed cell death, is essential for multicellular organisms.
• DNA fragmentation factor (DFF) mediates nuclear DNA degradation during apoptosis in mammalian cells.
• DFF consists of two subunits: DFFA (inhibitor of caspase-activated DNase) and DFFB (caspase-activated DNase).

Purpose of the Study:

• To investigate the evolutionary history of the genes encoding DFFA and DFFB.
• To determine the ancestral presence and conservation of DFF components in early metazoans.
• To understand the evolutionary trajectory of the apoptosis system.

Main Methods:

• Comparative genomics was employed to identify orthologs of DFFA and DFFB across various species.
• Phylogenetic analysis was used to trace the evolutionary history of these genes.
• Sequence analysis was performed to assess the conservation of critical functional domains and residues.

Main Results:

• Orthologs of DFFA and DFFB were found in cnidarians (Nematostella vectensis), vertebrates, and insects.
• These genes were notably absent in urochordates, echinoderms, and nematodes.
• Conserved domains for DFFA-DFFB interaction, caspase cleavage site in DFFA, and critical residues for DFFB endonuclease activity were identified in Nematostella.

Conclusions:

• The DFF system appears to be an ancient component of the eumetazoan apoptosis system, present in the common ancestor.
• The evolutionary analysis suggests that the cell death machinery has undergone degeneration in specific lineages.
• This ancient machinery's loss in certain groups, like nematodes, highlights evolutionary divergence in apoptosis pathways.