ATG gene duplication in vertebrates: evolutionary divergence and its functional implications

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Genetics

Background:

• Macroautophagy (autophagy) relies on ~20 autophagy-related (ATG) genes.
• Gene duplication in ATG genes significantly impacts autophagy pathway evolution, particularly in vertebrates.
• The precise timing and functional divergence of vertebrate ATG gene duplications remain unclear.

Purpose of the Study:

• To investigate the duplication timing of ATG genes near the vertebrate root.
• To analyze the evolutionary divergence patterns and functional differences between ATG paralogs.
• To establish a timeline for functional differentiation of duplicated ATG genes.

Main Methods:

• Comparative analysis of sequence and gene expression divergence between ATG paralogs.
• Categorization of evolutionary fates (e.g., functional retention, neofunctionalization, subfunctionalization).
• Assessment of autophagic function for specific paralogs (e.g., ULK1/2, BECN1/2).

Main Results:

• Most ATG genes likely duplicated via whole-genome duplication events near the vertebrate root.
• Asymmetric evolution observed in BECN, WIPI, and ATG16 paralogs, with one retaining ancestral function.
• ULK-1, GABARAP, and LC3 paralogs show patterns consistent with dosage sharing or hypofunctionalization.
• ATG9B underwent significant sequence divergence and expression reduction in mammals.
• Only BECN1, not BECN2, retains autophagic function; both ULK1 and ULK2 support autophagy.

Conclusions:

• Vertebrate ATG gene duplication occurred primarily through ancient whole-genome duplications.
• Paralogs exhibit diverse evolutionary trajectories, impacting autophagy pathway function.
• Functional divergence and evolutionary fates provide insights into the adaptation of autophagy across vertebrates.