A Phylogenetic Rate Parameter Indicates Different Sequence Divergence Patterns in Orthologs and Paralogs.

Area of Science:

• Molecular Evolution
• Bioinformatics
• Genomics

Background:

• Heterotachy, the variation of evolutionary rates across a protein sequence over time, is a known phenomenon in molecular evolution.
• Site-specific evolutionary rate shifts are often linked to functional changes in proteins.
• Understanding evolutionary patterns in orthologous (speciation) versus paralogous (gene duplication) genes is crucial for inferring protein function and evolution.

Purpose of the Study:

• To computationally compare sequence divergence patterns between orthologous and paralogous protein sequence alignments.
• To investigate the relationship between sequence divergence, evolutionary rate variation (heterotachy), and gene duplication events.
• To test the ortholog conjecture, which posits greater functional conservation in orthologous proteins compared to paralogous ones.

Main Methods:

• Analysis of thousands of protein sequence alignments from animal and plant proteomes.
• Phylogenetic analyses to infer sequence divergence (tree length) and site-specific evolutionary rates using a discrete gamma distribution (shape parameter α).
• Simulations under various protein evolution models to validate inference methods and correlations.

Main Results:

• Sequence divergence and the inferred site rate distribution uniformity (α parameter) are positively correlated under heterotachy.
• Both orthologous and paralogous genes show a positive correlation between divergence and α.
• Paralogous protein alignments exhibit a significantly greater increase in α with divergence compared to orthologous alignments, indicating more pronounced rate fluctuations.

Conclusions:

• The findings support the hypothesis that recently duplicated genes (paralogs) initially experience relaxed selection, leading to accelerated functional divergence and increased evolutionary rate heterogeneity.
• The study provides computational evidence consistent with the ortholog conjecture, suggesting that orthologs generally maintain more conserved functions than paralogs.
• This research enhances our understanding of how gene duplication and divergence shape protein evolution and functional conservation across species.