Dosage balance acts as a time-dependent selective barrier to subfunctionalization.

Area of Science:

• Evolutionary biology
• Genomics
• Molecular evolution

Background:

• Gene duplication drives genome expansion and the evolution of new gene functions.
• Duplicate genes are retained via mechanisms like dosage balance, subfunctionalization, and neofunctionalization.
• Understanding the interplay of these retention mechanisms is crucial for evolutionary studies.

Purpose of the Study:

• To model the interplay between subfunctionalization and dosage balance in duplicate gene retention.
• To investigate how dosage balance affects selective pressures on duplicate gene copies.
• To compare a new model incorporating dosage balance with a subfunctionalization-only model.

Main Methods:

• Developed a Subfunctionalization + Dosage-Balance (Sub+Dos) Markov model.
• Incorporated a biophysical framework to penalize fitness of stoichiometrically imbalanced proteins.
• Compared Sub+Dos model with a Subfunctionalization-Only (Sub-Only) model for whole-genome and small-scale duplications.

Main Results:

• Dosage balance acts as a time-dependent selective barrier to subfunctionalization after whole-genome duplication, delaying but increasing overall retention.
• In small-scale duplications, dosage balance accelerates subfunctionalization but reduces the proportion of retained duplicates.
• Selective pressures against imbalanced gene partners slow both subfunctionalization and nonfunctionalization rates.

Conclusions:

• Subfunctionalization of dosage-sensitive genes is not a neutral process.
• Dosage balance significantly impacts the dynamics and outcomes of duplicate gene retention.
• The findings provide insights into the evolutionary forces shaping gene family evolution.