Structure-informed evolutionary analysis of the meiotic recombination machinery

Area of Science:

• Evolutionary biology
• Molecular biology
• Genetics

Background:

• Proteins crucial for fertility, particularly those in meiotic homologous recombination, exhibit rapid sequence divergence.
• Understanding the evolutionary pressures driving this divergence is challenging due to complex interactions between sequence changes, protein structure, and physiological functions.

Purpose of the Study:

• To develop and apply sensitive methods for detecting positive or relaxed selection in meiotic recombination proteins.
• To integrate evolutionary analyses with structural and functional data to understand protein evolution.
• To investigate the evolutionary plasticity of the meiotic recombination machinery.

Main Methods:

• Comparative evolutionary analyses of meiotic recombination proteins across primates, rodents, birds, and budding yeasts.
• Mapping selection rate estimates onto predicted protein structures to identify regions under positive selection.
• Analyzing selection at structurally matched residues to detect variation masked by structural constraints.
• Cross-species complementation experiments in *Saccharomyces cerevisiae*.

Main Results:

• Identified protein regions likely experiencing positive selection by mapping evolutionary rates onto structures.
• Detected subtle sequence variations within conserved domains, indicating potential loss of constraints or adaptive changes.
• Found lineage- and paralog-specific enrichment of non-synonymous substitutions.
• Demonstrated that sequence variation in MSH4 impacts recombination proficiency in yeast.

Conclusions:

• Evolutionary plasticity is a conserved feature of meiotic recombination proteins.
• The developed approach offers a mechanistic framework for analyzing protein evolution, particularly for proteins with complex functional constraints.
• Sequence variation in key recombination proteins can influence fertility-related processes.