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Significance Phenotypic evolution is driven primarily by natural selection but the majority of differences between the genomes of related species are thought to be neutral. Because of this, linking differences in phenotype to underlying genetic changes is challenging. Here, we applied evolutionary sequence analysis methods to comprehensively identify sites that evolved under positive selection in mammals and used available protein structures to link them to molecular mechanisms. This allowed us to detect clusters of positively selected sites in proteins involved in immunity, as well as enzymes that detoxify foreign chemicals, and demonstrate that those sites tend to localize to functionally important regions. Our findings suggest that, in addition to functional similarities, there are common structural features and mechanisms underpinning adaptive evolution.

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