Gene Birth Contributes to Structural Disorder Encoded by Overlapping Genes.

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• The same nucleotide sequence can encode multiple protein products by utilizing different reading frames.
• Overlapping genes are known to exhibit higher levels of intrinsic structural disorder (ISD) compared to non-overlapping genes, as observed in viral datasets.

Purpose of the Study:

• To investigate the reasons behind the elevated ISD in overlapping genes.
• To quantify the contributions of three hypotheses: intrinsic genetic code properties, recent de novo gene birth, and evolutionary constraint alleviation.

Main Methods:

• Comparative analysis of ISD levels in overlapping versus non-overlapping viral genes.
• Statistical modeling to attribute the elevation in ISD to different factors.

Main Results:

• The recency of de novo gene birth significantly contributes to the elevated ISD in overlapping viral gene regions.
• While individual reading frames within overlapping genes have different ISD tendencies, their net effect on ISD is neutral.
• Elevated ISD in older overlapping gene members predates the gene overlap, suggesting it aids in alleviating evolutionary constraints.

Conclusions:

• Recent de novo gene birth is the main driver of increased intrinsic structural disorder in overlapping genes.
• Evolutionary constraints and mutation biases also play roles in shaping ISD in overlapping gene regions.