TraitRateProp: a web server for the detection of trait-dependent evolutionary rate shifts in sequence sites.

Understanding species adaptation at the molecular level has been a central goal of evolutionary biology and genomics research. This important task becomes increasingly relevant with the constant rise in both genotypic and phenotypic data availabilities. The TraitRateProp web server offers a unique perspective into this task by allowing the detection of associations between sequence evolution rate and whole-organism phenotypes. By analyzing sequences and phenotypes of extant species in the context of their phylogeny, it identifies sequence sites in a gene/protein whose evolutionary rate is associated with shifts in the phenotype. To this end, it considers alternative histories of whole-organism phenotypic changes, which result in the extant phenotypic states. Its joint likelihood framework that combines models of sequence and phenotype evolution allows testing whether an association between these processes exists. In addition to predicting sequence sites most likely to be associated with the phenotypic trait, the server can optionally integrate structural 3D information. This integration allows a visual detection of trait-associated sequence sites that are juxtapose in 3D space, thereby suggesting a common functional role. We used TraitRateProp to study the shifts in sequence evolution rate of the RPS8 protein upon transitions into heterotrophy in Orchidaceae. TraitRateProp is available at https://traitrate.tau.ac.il/prop.