Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals

Area of Science:

• Evolutionary biology
• Molecular biology
• Structural biology

Background:

• Understanding environmental adaptation at the molecular level is key in evolutionary biology.
• Linking positive selection signatures to specific molecular mechanisms is challenging.

Purpose of the Study:

• To integrate sequence-based phylogenetic methods with structural information for mechanistic interpretation of positive selection.
• To investigate the spatial distribution of positively selected sites on protein structures.

Main Methods:

• Phylogenetic analysis of protein sequences.
• Mapping positively selected sites onto protein three-dimensional structures.
• Functional annotation of proteins exhibiting strong positive selection signals.

Main Results:

• Positively selected sites frequently colocalize in clusters on protein structures.
• These clusters often occur in functionally important protein regions, sometimes overriding conservation.
• Proteins with strong evidence of clustered positive selection are predominantly involved in immune response and metabolic functions.

Conclusions:

• Positive selection can act on structural clusters, offering new avenues for protein evolution modeling.
• Immune response and metabolic enzymes are key targets of adaptive evolution, driven by factors like pathogens and xenobiotics.