Compensatory Drift and the Evolutionary Dynamics of Dosage-Sensitive Duplicate Genes

Area of Science:

• Evolutionary genetics
• Molecular evolution
• Systems biology

Background:

• Dosage-balance selection maintains optimal combined expression of gene duplicates (paralogs).
• Understanding the evolutionary dynamics of paralogs under this selection is crucial for deciphering gene family evolution.

Purpose of the Study:

• To present and analyze the compensatory drift model for coevolving duplicate genes under dosage-balance selection.
• To investigate how gene expression divergence and neofunctionalization occur in paralogs over evolutionary time.

Main Methods:

• Development of the compensatory drift model to simulate gene duplication dynamics.
• Fitting the model to empirical data from sodium channel duplicates in teleost fish.
• Estimation of dosage-balance selection strength in observed gene families.

Main Results:

• Even with strong dosage-balance selection, individual paralog expression can diverge via drift.
• Divergence rates decrease with stronger stabilizing selection, larger mutation effects, or larger population sizes.
• Dosage-balance selection initially hinders but can later promote neofunctionalization.

Conclusions:

• Functionally redundant paralogs can undergo significant functional changes after extended periods of compensatory drift.
• The model provides insights into the evolutionary pathways of duplicate genes, including cases of neofunctionalization in electric fish.
• Dosage-balance selection plays a complex role in shaping paralog evolution, balancing constraint with the potential for innovation.