Overlapping genes and the proteins they encode differ significantly in their sequence composition from...

Area of Science:

• Genomics
• Evolutionary Biology
• Bioinformatics

Background:

• Overlapping genes encode multiple proteins from a single DNA sequence, posing evolutionary challenges.
• These genes are common in viruses and increasingly recognized in eukaryotes, but often missed in genome annotation.
• Accurate detection is crucial for understanding viral infection and evolutionary studies.

Purpose of the Study:

• To create a high-quality benchmark dataset of experimentally proven viral overlapping genes.
• To analyze the evolutionary and compositional characteristics of overlapping genes.
• To investigate the potential role of amino acid composition in the prevalence and evolution of overlapping genes.

Main Methods:

• Assembled a dataset of 80 experimentally validated viral overlapping genes.
• Analyzed nucleotide and amino acid composition of overlapping versus non-overlapping genes.
• Utilized principal component analysis to identify compositional biases.

Main Results:

• Overlapping genes exhibit significantly different nucleotide and amino acid compositions compared to non-overlapping genes.
• Proteins encoded by overlapping genes are enriched in high-degeneracy amino acids and depleted in low-degeneracy ones.
• A consistent composition bias was observed across most overlapping genes, including six mammalian examples.

Conclusions:

• A near-universal amino acid composition bias may facilitate the origin or evolution of overlapping genes.
• The findings highlight the importance of identifying overlapping genes for accurate genomic and evolutionary analyses.
• This study provides a valuable resource for future research on overlapping genes in various organisms.